Functionalized biomicroelectromechanical systems sensors for force response study at local adhesion sites of single living cells on substrates.

We present a method of measuring force response of a single living cell, attached to a substrate, in situ, by a functionalized microelectromechanical systems sensor that applies local deformation on the cell. The sensor is a single crystal silicon microcantilever beam with prescribed shape and geometry, and is coated by a thin layer of fibronectin. It is brought in contact with a cell to form adhesion cites, and is then moved by a piezoactuator to deform the cell locally. The force is transmitted from the adhesion site(s) on the cantilever to the sites on the substrate through the cytoskeleton. The interaction force between the cell and the cantilever is measured from the deformation of the cantilever and its spring constant, which can be obtained by several independent means. The force and the cell deformation can be 10 s of nano-Newtons and micrometers, respectively. We demonstrate the method using two families of force sensors with spring constants of 18 and 0.4 nN/microm. Several cells, endothelial and fibroblast, are deformed by tens of micrometers until the adhesion sites failed. Their force-deformation response shows strong linearity. Several possible mechanisms are discussed to explain the linear response.