Research.RecognitionAndBioAdhesion History

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We use [[SurfaceForceApparatus|surface forces apparatus]] measurements to directly quantify how colloidal surface forces alter binding to immobilized ligands. A recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]] showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how proteins in immunity recognize and bind pathogens. We also determined how genetic variations alter pathogen recognition, in ways that correlate with differences in human susceptibility to viral infections.
to:
[[SurfaceForceApparatus|Surface forces apparatus]] measurements directly quantify how colloidal surface forces alter the recognition of immobilized ligands. A recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]] determined how ligand density and lateral mobility, in concert with structural flexibility affects how proteins in immunity recognize and bind pathogens. We also determined how genetic variations alter pathogen recognition, in ways that correlate with differences in human susceptibility to viral infections.
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Unlike binding in solution, the interfacial environment can dramatically alter the molecular recognition of surface-bound ligands in a variety of contexts including biosensors, biomaterials, drug delivery, and biology.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase interactions.  Lateral mobility on membranes also affects apparent affinities, particularly for multi-valent receptors.  We use different analytical and biophysical approaches to understand the fundamental mechanisms underlying these effects as well as surface design rules for materials that preserve the function of immobilized biomolecules or enhance, for example, pathogen recognition. 
to:
Unlike binding in solution, the interfacial environment can dramatically alter the molecular recognition of surface-bound ligands in a variety of contexts including biosensors, biomaterials, drug delivery, and biology.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase interactions.  Lateral mobility on membranes also affects apparent affinities, particularly for multi-valent receptors.  We use different analytical and biophysical approaches to understand the fundamental mechanisms underlying these effects as well as design rules for materials that preserve the function of immobilized biomolecules or enhance, for example, pathogen recognition. 
Changed line 3 from:
Unlike binding in solution, the interfacial environment can dramatically alter the molecular recognition of surface-bound ligands in a variety of contexts including biosensors, biomaterials, drug delivery, pathogen infectivity, and biology.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase interactions.  Lateral mobility on membranes also affects apparent affinities, particularly for multi-valent receptors.  We use different analytical and biophysical approaches to understand the fundamental mechanisms underlying these effects as well as surface design rules for materials that preserve the function of immobilized biomolecules or enhance, for example, pathogen recognition. 
to:
Unlike binding in solution, the interfacial environment can dramatically alter the molecular recognition of surface-bound ligands in a variety of contexts including biosensors, biomaterials, drug delivery, and biology.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase interactions.  Lateral mobility on membranes also affects apparent affinities, particularly for multi-valent receptors.  We use different analytical and biophysical approaches to understand the fundamental mechanisms underlying these effects as well as surface design rules for materials that preserve the function of immobilized biomolecules or enhance, for example, pathogen recognition. 
Changed line 3 from:
Unlike binding in solution, the molecular recognition of surface-bound ligands is often substantially altered by the interfacial environment.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase binding.  Lateral mobility on fluid membranes also affects apparent affinities, particularly for multi-valent receptors.  We are using different approaches to determine the impact of the surface environment on biological recognition in several applications including infectivity and drug delivery.
to:
Unlike binding in solution, the interfacial environment can dramatically alter the molecular recognition of surface-bound ligands in a variety of contexts including biosensors, biomaterials, drug delivery, pathogen infectivity, and biology.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase interactions.  Lateral mobility on membranes also affects apparent affinities, particularly for multi-valent receptors.  We use different analytical and biophysical approaches to understand the fundamental mechanisms underlying these effects as well as surface design rules for materials that preserve the function of immobilized biomolecules or enhance, for example, pathogen recognition. 
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Biomolecular recognition at interfaces is widespread in both biology and biotechnology.  Unlike binding in solution, receptor binding to surface-bound ligands is often substantially altered by the interfacial environment.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase bindingLateral mobility on fluid membranes also affects apparent affinities, particularly for multi-valent receptors.  We are using different approaches to address how these factors impact biological recognition in several applications including infectivity and drug delivery.

To address this, we use [[SurfaceForceApparatus|surface forces apparatus]] measurements to directly quantify how colloidal surface forces alter binding to immobilized ligands. A recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we
showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how proteins in immunity recognize and bind pathogens. We also determined how genetic variations alter pathogen recognition, in ways that correlate with differences in human susceptibility to viral infections.
to:
Unlike binding in solution, the molecular recognition of surface-bound ligands is often substantially altered by the interfacial environment.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase binding.  Lateral mobility on fluid membranes also affects apparent affinities, particularly for multi-valent receptorsWe are using different approaches to determine the impact of the surface environment on biological recognition in several applications including infectivity and drug delivery.

We use [[SurfaceForceApparatus|surface forces apparatus]] measurements to directly quantify how colloidal surface forces alter binding to immobilized ligands. A recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]]
showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how proteins in immunity recognize and bind pathogens. We also determined how genetic variations alter pathogen recognition, in ways that correlate with differences in human susceptibility to viral infections.
Changed lines 10-14 from:
This aspect of our research uses multi-scale approaches to define relationships between molecular structure, mechanical strengths of biomolecular linkages, binding kinetics, and cell adhesion.  A combination of molecular dynamics simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identify relationships between the protein-ligand bond chemistry, the strength of biomolecular bonds and the dynamics and strength of cell adhesion.

For example, [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system identified key load bearing amino acids in the binding interface, and experimentally verified his predictions with point mutations in one of the proteins.  Subsequent molecular force measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to the protein-mediated adhesion.

Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
to:
This aspect of our research uses multi-scale approaches to define relationships between molecular structure, mechanical strengths of protein bonds, binding kinetics, and cell adhesion.  A combination of molecular dynamics simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identifies relationships between the protein-ligand bond chemistry, the strength and the dynamics of bond formation/rupture, and cell adhesion.

For example, [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system identified key load bearing amino acids in the binding interface. The predicted critical bonds were experimentally verified by molecular force measurements [[http://www.jbc.org/content/282/8/5589.long|simulation]]. These and similar findings are being used to determine how macromolecular structure governs mechanical function in cell adhesion and transmembrane information transfer.

As a model system, we focus on cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
Changed line 14 from:
Ongoing studies focus on the cell-cell adhesion proteins cadherins that are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
to:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
Changed lines 3-6 from:
Biomolecular recognition at interfaces is widespread in both biology and biotechnology.  Unlike binding in solution, receptor binding to surface-bound ligands is often substantially altered by the interfacial environment.  Interfacial forces alter the kinetics and binding affinities relative to solution phase binding.  Lateral mobility on fluid membranes also alters apparent affinities, particularly for multi-valent receptors.  These issues directly impact a range of topics from viral infectivity to targeted drug delivery. 

We quantitatively explore the impact of the interfacial environment
and ligand presentation on recognition at interfaces.  Studies use the [[SurfaceForceApparatus|surface forces apparatus]] to directly quantify how colloidal surface forces alter binding to immobilized ligands. In a recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how multivalent receptors in immunity recognize and bind pathogens. We also determined how genetic variations in a related protein alter its ability to recognize pathogens. The latter structural variations correlate with differences in human susceptibility to viral infections.
to:
Biomolecular recognition at interfaces is widespread in both biology and biotechnology.  Unlike binding in solution, receptor binding to surface-bound ligands is often substantially altered by the interfacial environment.  Surface forces and even the molecular length can alter the kinetics and binding affinities relative to solution phase binding.  Lateral mobility on fluid membranes also affects apparent affinities, particularly for multi-valent receptors.  We are using different approaches to address how these factors impact biological recognition in several applications including infectivity and drug delivery.

To address this, we use [[SurfaceForceApparatus|surface forces apparatus]] measurements to directly quantify how colloidal surface forces alter binding to immobilized ligands. A recent study published in
[[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how proteins in immunity recognize and bind pathogens. We also determined how genetic variations alter pathogen recognition, in ways that correlate with differences in human susceptibility to viral infections.
Changed lines 10-14 from:
We use a multi-scale approach to define relationships between molecular structure, mechanical strengths of biomolecular linkages, binding kinetics, and cell adhesion.  A combination of molecular dynamics simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identify relationships between the chemistry and mechanical strength of biomolecular bonds.

Marco Bayas (Biophysics) performed
[[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system that help bind killer cells to antigen presenting cells. He identified key load bearing amino acids in the binding interface, and experimentally verified his predictions with point mutations in one of the proteins.  Surface force measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to the protein-mediated adhesion.

Ongoing studies focus on the cell-cell adhesion proteins cadherins, which
are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
to:
This aspect of our research uses multi-scale approaches to define relationships between molecular structure, mechanical strengths of biomolecular linkages, binding kinetics, and cell adhesion.  A combination of molecular dynamics simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identify relationships between the protein-ligand bond chemistry, the strength of biomolecular bonds and the dynamics and strength of cell adhesion.

For example,
[[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system identified key load bearing amino acids in the binding interface, and experimentally verified his predictions with point mutations in one of the proteins.  Subsequent molecular force measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to the protein-mediated adhesion.

Ongoing studies focus on the cell-cell adhesion proteins cadherins that
are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
October 29, 2010, at 04:30 PM by 130.126.231.65 -
Changed lines 3-5 from:
Biomolecular recognition at interfaces is widespread in both biology and biotechnology.  Unlike binding in solution, receptor binding to surface-bound ligands is often substantially altered by the interfacial environment.  Interfacial forces alter both the kinetics and apparent binding affinities relative to solution phase binding.  Lateral mobility on fluid lipid membranes also alter apparent affinities, particularly by multi-valent receptors.  These issues directly impact a range of topics from viral infectivity to targeted drug delivery. 

Our work quantitatively explores the impact of the interfacial environment and ligand presentation on recognition at surfaces.  Studies use the [[SurfaceForceApparatus|surface forces apparatus]] to directly quantify how colloidal surface forces alter binding to immobilized ligands. In a recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects the capacity of multivalent receptors in immunity to recognize and bind pathogens. A subsequent study investigated how genetic variations in a related protein affect the extension of the receptor from the cell membrane and its ability to recognize pathogens. These structural variations correlate with differences in susceptibility to viral infections.
to:
Biomolecular recognition at interfaces is widespread in both biology and biotechnology.  Unlike binding in solution, receptor binding to surface-bound ligands is often substantially altered by the interfacial environment.  Interfacial forces alter the kinetics and binding affinities relative to solution phase binding.  Lateral mobility on fluid membranes also alters apparent affinities, particularly for multi-valent receptors.  These issues directly impact a range of topics from viral infectivity to targeted drug delivery. 

We quantitatively explore the impact of the interfacial environment and ligand presentation on recognition at interfaces.  Studies use the [[SurfaceForceApparatus|surface forces apparatus]] to directly quantify how colloidal surface forces alter binding to immobilized ligands. In a recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects how multivalent receptors in immunity recognize and bind pathogens. We also determined how genetic variations in a related protein alter its ability to recognize pathogens. The latter structural variations correlate with differences in human susceptibility to viral infections.
October 29, 2010, at 04:27 PM by 130.126.231.65 -
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In one example, Marco Bayas (Biophysics) performed [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system that help bind killer cells to antigen presenting cells. The simulations identified major load bearing amino acids in the binding interface.  We then experimentally tested point mutations at the CD2 interface that were predicted to impact protein adhesion.  Surface force apparatus measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to CD2-mediated adhesion.
to:
Marco Bayas (Biophysics) performed [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system that help bind killer cells to antigen presenting cells. He identified key load bearing amino acids in the binding interface, and experimentally verified his predictions with point mutations in one of the proteins.  Surface force measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to the protein-mediated adhesion.
September 01, 2010, at 09:21 AM by 130.126.230.170 -
Changed line 5 from:
Our work quantitatively explores the impact of the interfacial environment and ligand presentation on recognition at surfaces.  Studies use the [[SurfaceForceApparatus|surface forces apparatus]] to directly quantify how colloidal surface forces alter binding to immobilized ligands. In a recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein structure affects the capacity of multivalent receptors in immunity to recognize and bind pathogens. A subsequent study investigated how genetic variations in a related protein affect the extension of the receptor from the cell membrane and its ability to recognize pathogens. These structural variations correlate with differences in susceptibility to viral infections.
to:
Our work quantitatively explores the impact of the interfacial environment and ligand presentation on recognition at surfaces.  Studies use the [[SurfaceForceApparatus|surface forces apparatus]] to directly quantify how colloidal surface forces alter binding to immobilized ligands. In a recent study published in [[http://www.pnas.org/content/106/28/11524.long| PNAS]], we showed how ligand density and lateral mobility, in concert with structural flexibility in the protein affects the capacity of multivalent receptors in immunity to recognize and bind pathogens. A subsequent study investigated how genetic variations in a related protein affect the extension of the receptor from the cell membrane and its ability to recognize pathogens. These structural variations correlate with differences in susceptibility to viral infections.
September 01, 2010, at 09:20 AM by 130.126.230.170 -
Changed line 14 from:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent[[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern initial cell binding kinetics and intracellular signaling.
to:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern both initial cell binding kinetics and intracellular signaling.
September 01, 2010, at 09:20 AM by 130.126.230.170 -
Changed line 14 from:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions. In subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern initial cell binding kinetics.
to:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions, and mapped them to different structural regions of the protein. Subsequent[[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern initial cell binding kinetics and intracellular signaling.
September 01, 2010, at 09:18 AM by 130.126.230.170 -
Changed line 14 from:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  Using [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force measurements]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]], we identified and characterized different cadherin binding interactions. In subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern initial cell binding kinetics.
to:
Ongoing studies focus on the cell-cell adhesion proteins cadherins, which are critical for development and tissue generation. Cadherin dysfuction is linked to a number of human diseases.  [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302983/?tool=pubmed| Surface Force Apparatus]], [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367289/?tool=pubmed|Biomembrane Force Probe]], and [[http://www.jbc.org/content/283/42/28454.long|Atomic Force Microscopy]] measurements identified and characterized different cadherin binding interactions. In subsequent [[Research.MicropipetteManipulation|micropipette studies]] of cadherin-mediated binding kinetics between [[http://www.jbc.org/content/283/4/1848.long|single cell pairs]], we demonstrated that binding properties at the single molecule level govern initial cell binding kinetics.
September 01, 2010, at 09:16 AM by 130.126.230.170 -
Changed lines 10-12 from:
We use a multi-scale approach to define relationships between molecular structure, mechanical strengths of biomolecular linkages, binding kinetics, and cell adhesion.  A combination of atomistic simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identify relationships between the chemistry and mechanical strength of biomolecular bonds.

In one example, Marco Bayas (Biophysics) performed [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system that help bind killer cells to antigen presenting cells. The simulations identified major load bearing amino acids in the binding interface.  We then experimentally tested point mutations at the CD2 interface that were predicted to impact protein adhesion.  Surface force apparatus measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] simulation predictions and also quantified contributions of side chain interactions to CD2-mediated adhesion.
to:
We use a multi-scale approach to define relationships between molecular structure, mechanical strengths of biomolecular linkages, binding kinetics, and cell adhesion.  A combination of molecular dynamics simulations, single molecule force spectroscopy, cell binding measurements, and protein engineering uniquely identify relationships between the chemistry and mechanical strength of biomolecular bonds.

In one example, Marco Bayas (Biophysics) performed [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302789/?tool=pubmed|atomistic simulations]] of the forced rupture of the bond between two adhesion proteins in the immune system that help bind killer cells to antigen presenting cells. The simulations identified major load bearing amino acids in the binding interface.  We then experimentally tested point mutations at the CD2 interface that were predicted to impact protein adhesion.  Surface force apparatus measurements experimentally confirmed the [[http://www.jbc.org/content/282/8/5589.long|simulation]] predictions and also quantified contributions of side chain interactions to CD2-mediated adhesion.

Page last modified on October 01, 2011, at 02:36 PM