Long-range and long-term interferometric tracking by static and dynamic force-clamp optical tweezers

Optical tweezers are recognized single-molecule technique to resolve forces and motion on the molecular scale. Complex biological phenomena, such as cell differentiation and locomotion, require long range tracking capabilities with nanometer resolution over an extended period, to resolve molecular processes on the cellular scale. Here we introduce a real-time control of the microscope stage position to perform long-term tracking, with sub-millisecond resolution, of a bead attached to a neuron, preserving sub-nanometer sensitivity on a spatial range of centimeters, seven orders of magnitude larger. Moreover, the suitability of the system is tested by time- modulating the force-clamp condition to study the role of statically and dynamically applied forces in neuronal differentiation.