91社区's Seminar Series in Quantitative Life Sciences and Medicine
Sponsored by CAMBAM, QLS, MiCM and the Ludmer Centre
罢颈迟濒别:听"The interplay of structural and cellular biophysics controls clustering of multivalent molecules"
Speaker: Leslie Loew (University of Connecticut)
When:听Tuesday, November 6, 12-1pm
Where: McIntyre Building, Room 1027
听
Abstract: Dynamic molecular clusters are assembled through weak multivalent interactions and are platforms for cellular functions, especially receptor-mediated signaling. Using coarse-grain kinetic Langevin dynamics, we performed computational experiments on a prototypical ternary system modeled after membrane-bound nephrin, the adaptor Nck1 and the actin nucleation promoting factor NWASP. Steady state cluster size distributions favored stoichiometries that optimized binding, but still were quite broad. A balance of enthalpy and entropy limited the number of molecules per cluster, with complete annealing into a single complex being exceedingly rare. Domains close to binding sites sterically inhibited clustering much less than terminal domains because the latter effectively restrict access to the cluster interior. Increased flexibility of interacting molecules diminished clustering by shielding binding sites within compact conformations. Membrane association of nephrin increased the cluster size distribution in a density-dependent manner. These properties provide insights into how molecular ensembles function to localize and amplify cell signaling.
