MECHANICS COLLOQUIUM

FRIDAY 26 JANUARY 2007

2.30, LECTURE ROOM 6

CAMBRIDGE UNIVERSITY ENGINEERING DEPARTMENT

Biomechanics of the cytoskeleton: cell contractility and mechanosensitivity of cell adhesion

Vikram Deshpande

Cambridge University Engineering Dept.

Trumpington Street, Cambridge CB2 1PZ, UK.

A variety of in vitro cellular systems that model in vivo physiologic and pathologic processes have recently been developed. These systems such as arrays of micro-needles and micro-patterned substrates are used to quantitatively probe mechanical responses of cells to a variety of bio-chemo-mechanical stimuli. These studies have begun to reveal that mechanical coupling of the cell to its environment has implications for cell development, differentiation, disease, and regeneration. Key roles in molecular pathways are played by adhesion complexes and the actin/myosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. This seminar will focus on the contractility of the cytoskeletal network and the “inside-out” mechanism whereby cytoskeletal tension drives focal adhesion assembly.

The cytoskeletal contractility model accounts for the dynamic reorganization of the actin/myosin stress fibers and is motivated by three key bio-chemical processes: (i) an activation signal that triggers actin polymerization and myosin phosphorylation, (ii) the tension dependent assembly of the actin and myosin into stress fibers and (iii) the cross-bridge cycling between the actin and myosin filaments that generates the tension. Simple relations are proposed to model these coupled phenomena and a continuum model developed for simulating cell contractility. The mechanosensitivity of focal adhesion formation is motivated from thermodynamic considerations and a continuum framework developed in which the cytoskeletal forces drive the assembly of the focal adhesion multi-protein complexes.

The coupled cytoskeletal and adhesion models are shown to be capable of predicting key experimentally established characteristics including (a) the decrease in the forces generated by the cell with increasing substrate compliance, (b) the influence of cell shape and boundary conditions on the development of structural anisotropy, (c) the high concentration of the stress fibers at the focal adhesions and the (d) the ability of cells to detect chemical and mechanical heterogeneities in their environment.