Current research interests
1. Visualizing molecular forces in living cells by a reversible shearing DNA-based tension probe
Cells are highly dynamic in tissues, and their functions are constantly regulated by various forms of mechanical forces generated by the pushing, pulling and squeezing, both by other cells and the extracellular matrix (ECM). The mechanical forces generated by cells in tissues are substantial and can be easily in the range of many nN. Instead, the force per receptor is tiny, with its magnitude distributing from a few pN to tens of pN, but these molecular forces can precisely regulate the signal transduction process in time and space, thereby directly or indirectly controlling a number of biological responses such as cell differentiation, gene expression, and apoptosis. In the last decade, DNA-based tension sensors had made significant contributions to study the importance of mechanical forces in many biological systems. Albeit successful, one shortcoming of these techniques is their inaccessibility to reversibly measure receptor forces in a higher regime (i.e. >20-pN), which limited our understanding of the molecular details of mechano-chemo-transduction in living cells. We are developing a reversible shearing DNA-based tension probe (RSDTP) for probing molecular pN-scale forces between 4-60 pN transmitted by cells. Using these probes, we can easily distinguish the differences of force-bearing integrins without perturbing adhesion biology. We are particularly interested in understanding how cells sense and respond to mechanical forces at the molecular level.
Reversible shearing DNA-based tension probe and cellular force images
Reference: Li et al, A Reversible shearing DNA probe for visualizing mechanically strong receptors in living cells, Nature Cell Biology, 2021.
Movie 1: Revealing the magnitude and spatial dynamics of integrin forces in living cells with RSDTP.
(Top, 17-pN; middle, 45-pN; bottom, 56-pN).
Movie 2: Imaging of different levels of integrin force in real time with multiplexed RSDTP.