Prof. Vikram Deshpande
Department of Mechanical Engineering
University of California, Santa Barbara
Biomechanics of the Cytoskeleton:
Cell Contractility and Mechanosensitivity of Cell Adhesion
A variety of in vitro cellular systems that model in vivo physiologic and pathologic processes haverecently 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 will be shown to be capable of predicting a range of experimentally made observations with regards the coupling of the responses of cells with their mechanical and chemical environments.
Wednesday, January 30, 2008
Discovery Learning Center, Bechtel Collaboratory
12:00 noon – 1:00 pm