Learn More
Eukaryotic and prokaryotic cells use cytoskeletal proteins to regulate and modify cell shape. During cytokinesis or eukaryotic cell crawling, contractile forces are generated inside the cell to constrict the division site or to haul the rear of the cell forward, respectively. In many cases, these forces have been attributed to the activity of molecular(More)
We present a model describing friction due to the thermally activated formation and rupture of molecular bonds between two surfaces, with long molecules on one surface attaching to discrete or continuous binding sites on the other. The physical assumptions underlying this model are formalized using a continuum approximation resulting in a class of(More)
The ability for cells to sense and adapt to different physical microenvironments plays a critical role in development, immune responses, and cancer metastasis. Here we identify a small subset of focal adhesions that terminate fibers in the actin cap, a highly ordered filamentous actin structure that is anchored to the top of the nucleus by the LINC(More)
Elevated levels of inorganic phosphate (P(i)) are believed to inhibit muscular force by reversing myosin's force-generating step. These same levels of P(i) can also affect muscle velocity, but the molecular basis underlying these effects remains unclear. We directly examined the effect of P(i) (30 mM) on skeletal muscle myosin's ability to translocate actin(More)
Elevated levels of phosphate (Pi) reduce isometric force, providing support for the notion that the release of Pi from myosin is closely associated with the generation of muscular force. Pi is thought to rebind to actomyosin in an ADP-bound state and reverse the force-generating steps, including the rotation of the lever arm (i.e., the powerstroke). Despite(More)
A dynamical system is said to exhibit hysteresis if its current state depends on its history. Muscle shows hysteretic properties at constant length, such as residual force enhancement after stretch. There is no generally accepted explanation for residual force enhancement. Here we examine a very simple kinetic model for the interaction between actin and(More)
Tissue cells sense and respond to the stiffness of the surface on which they adhere. Precisely how cells sense surface stiffness remains an open question, though various biochemical pathways are critical for a proper stiffness response. Here, based on a simple mechanochemical model of biological friction, we propose a model for cell mechanosensation as(More)
Smooth muscle myosin is activated by regulatory light chain (RLC) phosphorylation. In the unphosphorylated state the activity of both heads is suppressed due to an asymmetric, intramolecular interaction between the heads. The properties of myosin with only one of its two RLCs phosphorylated, a state likely to be present both during the activation and the(More)
In contracting muscle, individual myosin molecules function as part of a large ensemble, hydrolyzing ATP to power the relative sliding of actin filaments. The technological advances that have enabled direct observation and manipulation of single molecules, including recent experiments that have explored myosin's force-dependent properties, provide detailed(More)
Muscle contracts due to ATP-dependent interactions of myosin motors with thin filaments composed of the proteins actin, troponin, and tropomyosin. Contraction is initiated when calcium binds to troponin, which changes conformation and displaces tropomyosin, a filamentous protein that wraps around the actin filament, thereby exposing myosin binding sites on(More)