Optical tweezers integrated surface plasmon resonance holographic microscopy for characterizing cell-substrate interactions under noninvasive optical force stimuli.

The rapid development of bio-mechanical research increases the significance of studying cell behaviors near the substrate under the force stimuli in a real-time manner. Here, we present an optical tweezers (OT) integrated surface plasmon resonance holographic microscopy (SPRHM) to realize the dynamical and in-situ characterizations of cell-substrate interactions with noninvasive optical force stimulations. Using the OT integrated SPRHM (OT-SPRHM), we dynamically manipulate the living cells by OT, and simultaneously, the phase-contrast surface plasmon resonance images of the living cells are obtained and the cell-substrate distance is determined via SPRHM. We show that OT-SPRHM has the advanced capabilities of measuring the optical force and its tiny variations applied to the K562 cells near the substrate. Also, we for the first time reveal the manipulation of the MC3T3-E1 cells by OT. Demonstrating its robustness, this technique provides a powerful tool to explore the responses of various biological specimens to the force stimuli along the cell-substrate interface in the bio-sensing area.