Microrheology of cytoskeleton networks

Sketch of 2-bead microrheology in polymer solutions. Two optical traps of different colors hold each one colloidal bead. In active microrheology, one bead is oscillated and the response of the other one is monitored, in passive microrheology, the correlated thermal fluctuations of both beds are traced.

We study the mechanical properties of cytoskeletal protein polymers and polymer networks with single-molecule micromechanical and with microrheology techniques with the goal of understanding the functional principles of the cytoskeleton, which plays crucial roles in processes such as cell division, cell locomotion, or cell growth, as well as mechano-sensing and signaling. Microrheology is a technique we pioneered about 10 years ago. With microrheology one can measure viscoelastic properties of soft materials in very small samples, using optically trapped micron-sized beads embedded in the material one studies. Sensitivity and bandwidth are high because one can use a focused laser for the detection of forces and displacements. Microrheology can be done passively, just observing thermal fluctuations, or actively, exerting oscillating forces on the trapped beads. One can also either use single beads or measure the correlated motions of pairs of beads. As simple model systems for the cytoskeleton we study in vitro reconstituted networks of semiflexible proteins such as actin or microtubules. Semiflexible polymers are a class of polymers that are frequently encountered in biological materials and are less well understood than flexible polymers. We study the length- and timescale dependent dynamic response of such networks and successively increase the complexity of the systems by adding crosslinkers and other regulatory agents. We have also sucessfully constructed a non-equilibrium model network consisting of actin and myosin motors that exhibits motor-driven fluctuations that are in certain ways very similar to those observed inside cells. (collaboration with F. MacKintosh, VU Amsterdam, A. Levine, UCLA)