Lele Laboratory-Nuclear Mechanics

Nuclear Mechanics

We are interested in how cytoskeletal forces position organelles in the cell, such as the nucleus. A current focus is on the mechanical interaction between the nucleus and the surrounding tensed actin cytoskeleton. Using molecular biology approaches(RNA interference), we knocked down the expression of a protein (nesprin-1) that links the nucleus to the tensed cytoskeleton. This caused a number of changes in cell function, which could all be explained by a simple model (see figure). We collaborate with Prof. Charles Thodeti on this project. Read the paper by Chancellor et al to learn more.

The nucleus balances part of the intracellular actomyosin forces through direct connections with F-actin (mediated by proteins like nesprin-1). If these connections are decreased (e.g. by knockdown of nesprin-1), the extra tension is balanced at new focal adhesions by the substrate, leading to higher cell traction and decreased migration speeds.

Relevant Publications

Chancellor TJ, Lee J, Thodeti C and Lele TP, “Actomyosin tension exerted on the nucleus through nesprin-1 connections influences endothelial cell adhesion, migration and cyclic strain induced reorientation”, Biophysical Journal, In Press.

Wu, J., Lee K, Dickinson RB and Lele TP (2010). How dynein and microtubules rotate the nucleus, Journal of Cellular Physiology (Accepted).

Design: Manali Matkar