Mechanobiology of Cardiac Sarcomere

Speaker : PANG Si Ming (Graduate Student, MBI, NUS)
Date : 22 Feb 2017, Wednesday
Time : 2pm
Venue : MBI, level 5 seminar rooms

Supervisor(s) : Prof YAN Jie

Abstract: Cardiac titin is one of the three filaments in cardiac sarcomere. During the relaxation of the sarcomere, the extension of titin increases considerably, by more than 20% of its total length, resulting in a build-up of tension. The portion of titin that is mainly responsible for this change in its extension is in the I-Band region, which contains numerous (43 or more) Ig-like domains with well-defined structures, and 3 less-structured domains namely N2B, N2A, and PEVK. Recent studies have found that force is able to promote the Ig-like domains to undergo stepwise transition, raising the question of the roles of these transitions in buffering the tension build-up in titin. In addition, the N2B domain is found to interact with the four-and-a-half-Lim protein (FHL), and this interaction is increased with truncated titin which is under higher tension. This raises the question on N2B-FHL as being part of mechanosignalling process. Its mechanism, however, remains unknown. This proposal aims to investigate the mechano- transduction and signalling mechanisms in the cardiac titin by using computational simulation and magnetic tweezers. The force-dependent folding/unfolding rates of the Ig-like domains will be measured and used to simulate titin under physiological conditions to determine the role of Ig-like domains in buffering the tension. Moreover, the interaction between the various domains and their binding partners will be looked at while subjected to forces within the physiological range to better understand its mechanisms.

ALL EXCEPT PANEL ARE EXCUSED FOR CLOSE DOOR EXAMINATION