Mechanotransduction at the Cell Surface and Methods to Study Receptor Forces

Cells squeeze, pull, and tug on their surroundings and on one another, exerting molecular forces through specific receptors. These forces are incredibly small – at the scale of tens of piconewtons (pN). Although small in magnitude, these molecular forces can have profound biological impacts in many processes including the fate of differentiating stem cells, T cell response to antigen, cell division, cancer metastasis, and blood clotting. Therefore, the ability to measure molecular forces within living cells is paramount. This chapter will describe molecular tension fluorescence microscopy (MTFM) where a conventional fluorescence microscope is used to map cellular forces with pN resolution by using a calibrated molecular force probe. The focus will be on nucleic acid-based force sensors since this is the most sensitive class of MTFM probes. Following an overview of the classic DNA force sensor, this chapter discusses the versatile development and application of DNA-based tools to study receptor mechanics.