Biophysical Society Thematic Meeting

Mechanobiology of Disease

Poster Abstracts

111

36-POS

Board 36

Force Transmission through the Microtubule Cytoskeleton

Matthias D. Koch

1,2

, Alexander Rohrbach

University of Freiburg, Freiburg, Germany,

Princeton University, Princeton, NJ, USA.

The eukaryotic cytoskeleton is a complex and dynamic network that regulates important cellular

functions and is driven by a large variety of forces or mechanical stimuli. Due to their

mechanical rigidity, microtubules are able to transport such stimuli, which allows integrating

distant regions of a cell nearly instantaneously. This is relevant for the response to pressure,

gravity, or osmotic changes and during mechanotransduction, a critical process during many

severe diseases such as deafness or cancer.

So far, only equilibrium mechanical properties of single microtubules have been characterized.

Since intra- and extracellular forces occur on a brought range of time scales, we fill this void by

using an in vitro bottom-up approach to determine the frequency response of single microtubules

and small networks thereof that mimic the basic cytoskeletal structure. We combine a label-free

darkfield imaging technique with multiple time-shared optical tweezers to flexibly construct and

force-probe such networks with a well-defined, user-selected geometry over a broad frequency

range.

We report on a length dependent stiffening of individual microtubules above a physiologically

relevant transition frequency between 1–30Hz due to the excitation of higher order bending

modes. This increased transport efficiency for high frequencies can be regarded as a mechanical

high-pass filter with a tunable cutoff frequency, e.g., allowing the cell to react to rapid

fluctuations at distant sites. Furthermore, we identify and relate different mechanical responses

for different network geometries to different functions inside the cell. Triangular networks, for

example, display a comparatively high stiffness even for low frequencies and resemble a load

bearing scaffold protecting the nucleus. The mechanistic comparison between basic network

geometries, the known cytoskeletal topologies and the general function of different cell lines will

substantially strengthen our understanding of the function and structure of the cytoskeleton, both

during health and disease.