MECHANORESPONSIVE BEHAVIORS OF ACTIN CYTOSKELETAL PROTEINS IN CELL SHAPE CHANGE PROCESSES
Embargo until
2019-12-01
Date
2018-10-04
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Publisher
Johns Hopkins University
Abstract
For specialized cell function, as well as active cell behaviors like division, migration, and tissue development, cells must undergo dynamic changes in shape. To complete these processes, cells integrate chemical and mechanical signals to direct force production. At the core of cell shape change is the ability of the cell’s machinery to sense mechanical forces and tune the force-generating machinery as needed. Force-sensitive cytoskeletal proteins, including myosin II motors and actin crosslinkers, such as alpha-actinin and filamin, accumulate in response to internally generated and externally imposed mechanical stresses, endowing the cell with the ability to discern and respond to mechanical cues. The physical theory behind how these proteins display mechanosensitive accumulation has allowed us to predict paralog-specific behaviors of different crosslinking proteins and identify a zone of optimal actin-binding affinity that allows for mechanical stress-induced protein accumulation. It also allowed us to uncover a regulatory mechanism that utilizes the biphasic nature of mechanoresponse to tune the myosin II mechanoresponsiveness in mammalian cells. These molecular mechanisms coupled to the mechanical feedback systems ensure robust shape change, but if they go awry, they are poised to promote disease states, such as cancer cell metastasis and loss of tissue integrity.
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Keywords
myosin II, mechanoresponse, biophysics