Experimental Soft Condensed Matter Group
Harvard University, Prof. D. A. Weitz

Microtubule Mechanics in Cells

Cell migration, division, and contractility all involve force transmission through the cytoskeleton. A full understanding of the forces experienced by the structural elements of the cytoskeleton and their mechanical response is therefore essential for understanding a variety of fundamental biological processes. Mechanical studies have largely focused on the actin filament component of the cytoskeleton, however very little is known about the mechanical role of the MTs that are embedded in the actin network. This is particularly important since MTs are two orders of magnitude stiffer than actin filaments (see our studies of thermally fluctuating MTs where we measure the bending stiffness of MTs). On the left is a picture of the MT network in an adherent cell showing the high curvature of MTs (arrowheads), which suggests that MTs are not simply passive structural elements. We’d like to understand why they bend so much in cells and how this bending is related to the actin structures in which the MTs are embedded.

One of the ways we study the mechanical response of MTs in cells is the obvious one: we poke them and see what happens. We use fine glass microneedles to compressively load MTs at the cell periphery. In the picture on the right, the arrow points to the tip of the needle which is positioned next to a straight MT in the cell that we visualize using GFP-tubulin. In the sequence below, the tip of the needle is indicated with a white dot. As the needle pushes down, the MT buckles into a short wavelength shape (try this with your own cells by pinching yourself). Notice that this is different than what usually happens when you compress a rod! (try compressing a wooden coffee stirrer – it always goes into the long wavelength mode)

In general, when a MT bends it has to push the surrounding network out of the way. It is this coupling that generates the interesting buckling response shown above. The physics of this can be illustrated with a fun macroscopic experiment. If you compress a thin plastic rod embedded in gelatin (try this at home with thick fishing line sitting in Jell-O… let me know how it goes!), the rod buckles into short wavelength wrinkles, as shown in the picture on the right. The wavelength here is about 1cm. If you use fishing line that is thinner (so that the bending stiffness is smaller) then the wavelength will get smaller. The short wavelength buckling in MTs is due to exactly the same coupling between rod bending and surrounding network deformation! So the cell really is a composite material and the response of the MT to any deformation reflects this.

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On this project we work with engineers in Kit Parker’s lab, biologists in Don Ingber’s Lab, as well as our theorist friends L.Mahadevan and Fred MacKintosh

Cliff Brangwynne
Division of Engineering and Applied Science
Harvard University
9 & 15 Oxford Street, McKay Laboratory
Cambridge, MA 02138
617-496-8666
brangwyn@fas.harvard.edu