Cytoskeletal filament and intracel lular cargo dynamics facilitated by motor proteins role of activity and a catch bonded dynein

Abstract

The cytoskeleton of the cell is a highly complex, dynamic and adaptive system newlineof semiand#64258;exible and#64257;laments with their associated motor proteins and cross-linkers. It newlinegenerates internal stresses and responds to external ones, intermediates cell signal- newlineing, ensures the structural integrity and morphology of the cell and helps in the newlinespatial organization of cellular contents. This dynamic regulation is eand#64256;ected by the newlinecoordination of the diand#64256;erent cytoskeletal components : polymeric and#64257;laments such as newlinemicrotubules, actin and intermediate and#64257;laments; cross-linker proteins such as fascin newlineand and#945;-actinin; and motor proteins such as dynein, kinesin and myosin. newlineMuch of the physical understanding of the components of cytoskeletal network newlinehave been obtained through in-vitro experiments on cytoskeletal extracts. In a bead newlineassay a cytoskeletal and#64257;lament is irreversibly attached to a substrate, while the motor newlineproteins moving on the and#64257;lament are attached to a bead which is optically trapped. newlineOn the other hand, in a gliding assay setup, the geometry is inverted. Here, the newlinecargo domains of motor proteins are irreversibly adsorbed on a glass substrate, while newlinetheir and#64257;lament binding domains attach to the complimentary cytoskeletal and#64257;lament. In newlinethe presence of ATP, the motors move in a directed fashion along the length of the newlineand#64257;lament before detachment. This results in a gliding movement of the cytoskeletal newlineand#64257;lament in the opposite direction. Apart from a wealth of information on single motor newlineprotein movement and force generation, motility assays have revealed the emergence newlineof collective motion in high densities of such and#64257;laments leading to the formation of newlineclusters, swirls and interconnected bands. Within these in-vitro settings, it is possible newlineto ask theoretical questions regarding both the role of individual motor proteins and newlinetheir cooperative dynamics, in controlling the dynamics of the cargo/and#64257;lament that newlinethey bind/unbind to/from and therefore make falsiand#64257;able predictions amenable to newlineexperimental veriand#64257;cations.