Bidirectional allostery mechanism of catch-bond effect in cell adhesion

Evolving roles and dynamics for catch and slip bonds during adhesion cluster maturation

Focal adhesions are the loci of cellular adhesion to the extracellular matrix. At these sites, various integrins forge connections between the intracellular cytoskeleton and the outside world: large patches of multiple types of integrins together grip hold of collagen, fibronectin and other extracellular matrix components. The mixture of integrins composing the FA will, in general, contain both slip bond integrins and catch bond integrins---bonds whose lifetime increases with applied load and bonds for whom it decreases when forced. Prior work suggests that catch bonds are essential for proper…

Plasticity of hydrogen bond networks regulates mechanochemistry of cell adhesion complexes

Mechanical forces acting on cell adhesion receptor proteins regulate a range of cellular functions by formation and rupture of non-covalent interactions with ligands. Typically, force decreases the lifetimes of intact complexes (slip-bonds), making the discovery that these lifetimes can also be prolonged ("catch-bonds"), a surprise. We created a microscopic analytic theory by incorporating the structures of selectin and integrin receptors into a conceptual framework based on the theory of stochastic equations, which quantitatively explains a wide range of experimental data (including catch-bon…

Phenomenological and microscopic theories for catch bonds

Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has lead to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we assess the successes and limitations of such theories in explaining experimental data. The most wide…

Novel Catchbond mediated oscillations in motor-microtubule complexes

Generation of mechanical oscillation is ubiquitous to wide variety of intracellular processes. We show that catchbonding behaviour of motor proteins provides a generic mechanism of generating spontaneous oscillations in motor-cytoskeletal filament complexes. We obtain the phase diagram to characterize how this novel catch bond mediated mechanism can give rise to bistability and sustained limit cycle oscillations and results in very distinctive stability behaviour, including bistable and non-linearly stabilised in motor-microtubule complexes in biologically relevant regimes. Hitherto, it was th…

载荷下生物分子黏附的通用自稳定机制

A generic self-stabilization mechanism for biomolecular adhesions under load

受细胞黏着斑启发，提出一种无需主动反馈的通用分子机制，通过黏附分子构象变化与储库动态交换实现非平衡条件下的载荷驱动自稳定，从而稳健延长黏附寿命，并自然适用于含 talin 和 vinculin 的细胞黏附。

Force-driven growth of intercellular junctions

Mechanical force regulates the formation and growth of cell-cell junctions. Cadherin is a prominent homotypic cell adhesion molecule that plays a crucial role in establishment of intercellular adhesion. It is known that the transmitted force through the cadherin-mediated junctions directly correlates with the growth and enlargement of the junctions. In this paper, we propose a physical model for the structural evolution of cell-cell junctions subjected to pulling tractions, using the Bell-Dembo-Bongard thermodynamic model. Cadherins have multiple adhesive states and may establish slip or catch…