Скачать или смотреть Dr Rafael Tapia-Rojo Mechanochemical regulation of focal adhesion proteins

Rafael Tapia-Rojo speaks at the Imperial College Physics of Life Seminar series
https://www.imperial.ac.uk/physics-of...

Mechanochemical regulation of focal adhesion proteins
Mechanical forces direct many cellular processes, including motility, differentiation, or development. Cells sense forces imposed by their microenvironment and these mechanical cues are decoded to regulate mechanosensitive gene transcription programs that govern the cellular response to the initial mechanical stimulus. From a molecular perspective, such mechanotransduction processes are underpinned by the mechanical response of specialized force-sensing proteins, which are directly subjected to the forces transmitted from the extracellular environment. A protein under force undergoes conformational changes, which can expose previously cryptic binding sites, or regulate the reactivity of key amino acids, providing molecular mechanisms to convert mechanical cues into biochemical responses. Therefore, to gain a molecular understanding of mechanotransduction processes, it is essential to measure how the key force-sensing proteins respond to physiologically relevant forces and, in turn, how their force-dependent dynamics regulate signaling events such as binding of protein partners and posttranslational modifications. However, experimental limitations have largely precluded the study of force-sensing proteins under biologically relevant forces, particularly as the key molecular events typically occur at very low forces and over long timescales.

We have recently developed novel single-molecule magnetic tweezers instrumentation capable of measuring protein dynamics under low forces and over extended timescales. Here, I will present how we apply this instrumentation to study the dynamics, interactions, and mechanochemistry of key focal adhesion proteins, including talin, vinculin, and focal adhesion kinase.