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Soft matrices suppress cooperative behaviors among receptor-ligand bonds in cell adhesion.

Qian J, Gao H - PLoS ONE (2010)

Bottom Line: The fact that biological tissues are stable over prolonged periods of time while individual receptor-ligand bonds only have limited lifetime underscores the critical importance of cooperative behaviors of multiple molecular bonds, in particular the competition between the rate of rupture of closed bonds (death rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster.In the present paper, we report a more striking effect that, irrespective of stress concentration, soft matrices also suppress the birth rate in a bond cluster by increasing the local separation distance between open bonds.This is shown by theoretical analysis as well as Monte Carlo simulations based on a stochastic-elasticity model in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial force/separation are unified in a single modeling framework.

View Article: PubMed Central - PubMed

Affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America.

ABSTRACT
The fact that biological tissues are stable over prolonged periods of time while individual receptor-ligand bonds only have limited lifetime underscores the critical importance of cooperative behaviors of multiple molecular bonds, in particular the competition between the rate of rupture of closed bonds (death rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster. We have recently shown that soft matrices can greatly increase the death rate in a bond cluster by inducing severe stress concentration near the adhesion edges. In the present paper, we report a more striking effect that, irrespective of stress concentration, soft matrices also suppress the birth rate in a bond cluster by increasing the local separation distance between open bonds. This is shown by theoretical analysis as well as Monte Carlo simulations based on a stochastic-elasticity model in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial force/separation are unified in a single modeling framework. Our findings not only are important for understanding the role of elastic matrices in cell adhesion, but also have general implications on adhesion between soft materials.

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Related in: MedlinePlus

A stochastic-elastic model of focal contact demonstrating the effect of cell/matrix compliance.(A) A single adhesion patch between two elastic media (cell and extracellular matrix) subjected to a uniform tensile stress directly applied along the interface. In this case, the applied load is nominally equally shared among all bonds, independent of the system elasticity. (B) The elastic recoil at open bonds increasing the surface separation at these bond locations and suppressing receptor/ligand rebinding that is necessary for stable adhesion. (C) Bond transition between closed and open states at force-dependent dissociation and separation-dependent association rates.
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pone-0012342-g001: A stochastic-elastic model of focal contact demonstrating the effect of cell/matrix compliance.(A) A single adhesion patch between two elastic media (cell and extracellular matrix) subjected to a uniform tensile stress directly applied along the interface. In this case, the applied load is nominally equally shared among all bonds, independent of the system elasticity. (B) The elastic recoil at open bonds increasing the surface separation at these bond locations and suppressing receptor/ligand rebinding that is necessary for stable adhesion. (C) Bond transition between closed and open states at force-dependent dissociation and separation-dependent association rates.

Mentions: For failure of a multiple-bond adhesion, one must take into account the fact that individual bonds can rebind after they break, until the whole adhesion is detached. The analysis of Evans & Ritchie [20] did not consider such rebinding, but theoretical considerations by Seifert [25] indicated that bond rebinding can greatly enhance the adhesion lifetime. In a cluster made of parallel bonds, a specific pair of bond can break and reform multiple times as long as there exist unbroken cross-bridges between the surfaces. For a ligand on a substrate surface and a receptor tethered to a cell wall by a linear spring with stiffness and rest length , the binding or rebinding rate can be assumed to depend on the cell-substrate surface separation as [26]–[29](2)where is the thermal energy ( at physiological temperature), is a reference association rate when the receptor-ligand pair are within a binding radius , and is the partition function for the receptor confined in a harmonic potential between and (Fig. 1C) [28].


Soft matrices suppress cooperative behaviors among receptor-ligand bonds in cell adhesion.

Qian J, Gao H - PLoS ONE (2010)

A stochastic-elastic model of focal contact demonstrating the effect of cell/matrix compliance.(A) A single adhesion patch between two elastic media (cell and extracellular matrix) subjected to a uniform tensile stress directly applied along the interface. In this case, the applied load is nominally equally shared among all bonds, independent of the system elasticity. (B) The elastic recoil at open bonds increasing the surface separation at these bond locations and suppressing receptor/ligand rebinding that is necessary for stable adhesion. (C) Bond transition between closed and open states at force-dependent dissociation and separation-dependent association rates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2925891&req=5

pone-0012342-g001: A stochastic-elastic model of focal contact demonstrating the effect of cell/matrix compliance.(A) A single adhesion patch between two elastic media (cell and extracellular matrix) subjected to a uniform tensile stress directly applied along the interface. In this case, the applied load is nominally equally shared among all bonds, independent of the system elasticity. (B) The elastic recoil at open bonds increasing the surface separation at these bond locations and suppressing receptor/ligand rebinding that is necessary for stable adhesion. (C) Bond transition between closed and open states at force-dependent dissociation and separation-dependent association rates.
Mentions: For failure of a multiple-bond adhesion, one must take into account the fact that individual bonds can rebind after they break, until the whole adhesion is detached. The analysis of Evans & Ritchie [20] did not consider such rebinding, but theoretical considerations by Seifert [25] indicated that bond rebinding can greatly enhance the adhesion lifetime. In a cluster made of parallel bonds, a specific pair of bond can break and reform multiple times as long as there exist unbroken cross-bridges between the surfaces. For a ligand on a substrate surface and a receptor tethered to a cell wall by a linear spring with stiffness and rest length , the binding or rebinding rate can be assumed to depend on the cell-substrate surface separation as [26]–[29](2)where is the thermal energy ( at physiological temperature), is a reference association rate when the receptor-ligand pair are within a binding radius , and is the partition function for the receptor confined in a harmonic potential between and (Fig. 1C) [28].

Bottom Line: The fact that biological tissues are stable over prolonged periods of time while individual receptor-ligand bonds only have limited lifetime underscores the critical importance of cooperative behaviors of multiple molecular bonds, in particular the competition between the rate of rupture of closed bonds (death rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster.In the present paper, we report a more striking effect that, irrespective of stress concentration, soft matrices also suppress the birth rate in a bond cluster by increasing the local separation distance between open bonds.This is shown by theoretical analysis as well as Monte Carlo simulations based on a stochastic-elasticity model in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial force/separation are unified in a single modeling framework.

View Article: PubMed Central - PubMed

Affiliation: School of Engineering, Brown University, Providence, Rhode Island, United States of America.

ABSTRACT
The fact that biological tissues are stable over prolonged periods of time while individual receptor-ligand bonds only have limited lifetime underscores the critical importance of cooperative behaviors of multiple molecular bonds, in particular the competition between the rate of rupture of closed bonds (death rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster. We have recently shown that soft matrices can greatly increase the death rate in a bond cluster by inducing severe stress concentration near the adhesion edges. In the present paper, we report a more striking effect that, irrespective of stress concentration, soft matrices also suppress the birth rate in a bond cluster by increasing the local separation distance between open bonds. This is shown by theoretical analysis as well as Monte Carlo simulations based on a stochastic-elasticity model in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial force/separation are unified in a single modeling framework. Our findings not only are important for understanding the role of elastic matrices in cell adhesion, but also have general implications on adhesion between soft materials.

Show MeSH
Related in: MedlinePlus