Lifetime and Strength of Periodic Bond Clusters between Elastic Media under Inclined Loading

Division of Engineering, Brown University, Providence, Rhode Island, USA.
Biophysical Journal (Impact Factor: 3.97). 11/2009; 97(9):2438-45. DOI: 10.1016/j.bpj.2009.08.027
Source: PubMed


Focal adhesions are clusters of specific receptor-ligand bonds that link an animal cell to an extracellular matrix. To understand the mechanical responses of focal adhesions, here we develop a stochastic-elasticity model of a periodic array of adhesion clusters between two dissimilar elastic media subjected to an inclined tensile stress, in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial traction are unified in a single modeling framework. We first establish a fundamental scaling law of interfacial traction distribution and derive a stress concentration index that governs the transition between uniform and cracklike singular distributions of the interfacial traction within molecular bonds. Guided by this scaling law, we then perform Monte Carlo simulations to investigate the effects of cluster size, cell/extracellular matrix modulus, and loading direction on lifetime and strength of the adhesion clusters. The results show that intermediate adhesion size, stiff substrate, cytoskeleton stiffening, and low-angle pulling are factors that contribute to the stability of focal adhesions. The predictions of our model provide feasible explanations for a wide range of experimental observations and suggest possible mechanisms by which cells can modulate adhesion and deadhesion via cytoskeletal contractile machinery and sense mechanical properties of their surroundings.

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Available from: Jizeng Wang, Oct 05, 2015
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    • "Nicolas et al. (2004) and Nicolas and Safran (2006) proposed a mechanosensitive model to study the growth and shrinkage of focal adhesions within a range of force that can be tuned by the mechanical properties of the matrix. Gao et al. (2011) and Qian et al. (2009) developed a coupled stochastic–elastic model to reveal the physical mechanism of focal adhesion in cell–matrix interactions. Despite these important progresses, an interesting and fundamental issue remains unsolved: How does a cell sense the elasticity of ECM? "
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    ABSTRACT: Cells sense and respond to the elasticity of extracellular matrix (ECM) via integrin-mediated adhesion. As a class of well-documented mechanosenors in cells, integrins switch among inactive, bound, and dissociated states, depending upon the variation of forces acting on them. However, it remains unclear how the ECM elasticity directs and affects the states of integrins and, in turn, their cellular functions. On the basis of our recent experiments, a biomechanical model is proposed to reveal the role of ECM elasticity in the state-switching of integrins. It is demonstrated that a soft ECM can increase the activation level of integrins while a stiff ECM has a tendency to prevent the dissociation and internalization of bound integrins. In addition, it is found that more stable focal adhesions can form on stiffer and thinner ECMs. The theoretical results agree well with relevant experiments and shed light on the ECM elasticity-sensing mechanisms of cells.
    Journal of Biomechanics 01/2014; 47(6). DOI:10.1016/j.jbiomech.2014.01.022 · 2.75 Impact Factor
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    • "This coupling is typically modeled as a number of molecular springs in parallel, binding and unbinding to the substrate stochastically. Despite observation of elastic recoil events in a study of force-dependent integrin-cytoskeletal linkages [40], the molecular springs in general have been assumed to be rather brittle, breaking when stretched by no more than a few nanometers under a few picoNewtons of force [8,9,10,11,12,13]. This would cause the substrate to slip relative to the actin with a large apparent friction coefficient. "
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    ABSTRACT: Adhesions are multi-molecular complexes that transmit forces generated by a cell's acto-myosin networks to external substrates. While the physical properties of some of the individual components of adhesions have been carefully characterized, the mechanics of the coupling between the cytoskeleton and the adhesion site as a whole are just beginning to be revealed. We characterized the mechanics of nascent adhesions mediated by the immunoglobulin-family cell adhesion molecule apCAM, which is known to interact with actin filaments. Using simultaneous visualization of actin flow and quantification of forces transmitted to apCAM-coated beads restrained with an optical trap, we found that adhesions are dynamic structures capable of transmitting a wide range of forces. For forces in the picoNewton scale, the nascent adhesions' mechanical properties are dominated by an elastic structure which can be reversibly deformed by up to 1 µm. Large reversible deformations rule out an interface between substrate and cytoskeleton that is dominated by a number of stiff molecular springs in parallel, and favor a compliant cross-linked network. Such a compliant structure may increase the lifetime of a nascent adhesion, facilitating signaling and reinforcement.
    PLoS ONE 09/2013; 8(9):e73389. DOI:10.1371/journal.pone.0073389 · 3.23 Impact Factor
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    • "Although it is difficult to demonstrate experimentally owing to limited spatial resolution, force distribution in an elastic system is unlikely to be homogeneous. Theoretical models predict that, as adhesion size increases or substrate stiffness decreases, force localizes more and more strongly to the adhesion rim, eventually leading to a crack-like failure of the adhesion site (Qian et al., 2009; Gao et al., 2011). Such a mechanism would also work for apparent catch bonds, as they always become slip bonds at sufficiently high forces. "
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    ABSTRACT: Many essential cellular functions in health and disease are closely linked to the ability of cells to respond to mechanical forces. In the context of cell adhesion to the extracellular matrix, the forces that are generated within the actin cytoskeleton and transmitted through integrin-based focal adhesions are essential for the cellular response to environmental clues, such as the spatial distribution of adhesive ligands or matrix stiffness. Whereas substantial progress has been made in identifying mechanosensitive molecules that can transduce mechanical force into biochemical signals, much less is known about the nature of cytoskeletal force generation and transmission that regulates the magnitude, duration and spatial distribution of forces imposed on these mechanosensitive complexes. By focusing on cell-matrix adhesion to flat elastic substrates, on which traction forces can be measured with high temporal and spatial resolution, we discuss our current understanding of the physical mechanisms that integrate a large range of molecular mechanotransduction events on cellular scales. Physical limits of stability emerge as one important element of the cellular response that complements the structural changes affected by regulatory systems in response to mechanical processes.
    Journal of Cell Science 07/2012; 125(Pt 13):3051-60. DOI:10.1242/jcs.093716 · 5.43 Impact Factor
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