Betz Lab: Mechanics of cellular systems

GFP_actin growth cone

Actin dynamics of neuronal growth.

 


Living cells are amazing objects as they perform complex and well orchestrated functions on the micrometer size and in a highly noisy environment of constant Brownian motion. As on the micron length scale the typical energy scale of thermal movement (kT) and physiological process (ATP hydrolysis) merges, stochastic effects become an important contribution to the mechanical movement. From a physics point of view, the cells constantly consume energy not only to fulfill their tasks, but also to keep their organization. To study these biophysical and mechanical questions, we focus on a detailed quantification of the dynamical processes as well as the viscoelastic mechanical properties on timescales ranging from milliseconds to minutes.


In detail, we are interested in answering the following fundamental questions:
  • How can cells control and tune their mechanical properties?
  • How do cells mechanically interact in development, immune response and cancer progression?
  • What intracellular forces and mechanical changes happen during cell migration and cytokinesis?
  • What new statistical mechanics models can explain cytoskeletal mechanics and organization?

To answer these questions we aim at a detailed physical description of the mechanical processes that are used by living cells. For this we continuously develop new measurement techniques such as optical tweezers, high accuracy particle tracking, traction force microscopy, micropipette aspiration and UV laser ablation.




The three main axes of the lab



A) Active mechanics and organization of the cytoskeleton

We use active optical tweezers based microrheology to directly measure the viscoelastic material properties of living cells. This can be done using endogenous vesicles, or beads. By comparing the mechanical properties with the sponanteous fluctuations we can sperate the thermal and active forces a cell uses for transport and intracellular organization. By applying similar techniques using high precision interferometry we also gain detailed information about the membrane fluctuations of simple cells and cell blebs. This gives access to fundamental mechanical properties of the membrane, like membrane tension and bending modulus. We have successfully quantified the mechanical properties of living oocytes (under review), the active mechanics of erythrocytes (in revision) and cell blebs (Peukes, Biophysical Journal 2014).

Cell blebs

Dynamics of cellular blebs in M2 cells. The membrane (green) expands due to hydrostatic pressure generated by the acto-myosin cortex (red).

 

Cell blebs

Metastatic cancer cells (CT26,green) invading a biomimetic collagen matrix (red).

 

B) Mechanical interaction between cells and their 3D environment.

We are interested in the forces and deformations applied by migrating cells in a 3D extra cellular matrix (ECM) or tissue system. Cell migration serves a purpose that is often connected to the complex function of a whole organism. In development, cells need to migrate to ensure correct organism formation, while in immune response cells need to identify pathogens, transmit information and actively destroy bacteria or infected cells. In the context of cancer metastasis, the outgrowth of cancer cells is the onset of the formation of metastasis, which can be lethal for the organism. The focus of our work is to identify the mechanical interaction between the cells and their environment. This interaction can result in a reorganization of the passive ECM, or in a complex interaction with other, mechanically active or passive cells. To study these interactions we observe and manipulate single or multiple cells in biomimetic 3D collagen matrixes (Kopanska, Methods in cell Biology 2015) or to study single a,d collective migration in the developing zebrafish (collaboration Erez Raz).

C) Mechanics of reconstituted acto-myosin networks

To gain in depth access to the processes that allow cells to control their mechanical properties we follow a bottom up approach where we reconstitute cytoskeletal and membrane systems to directly study the mechanical properties. This approach exploits purified proteins to reproduce actin networks, bundles and biomimetic actin cortices. We can probe the mechanical properties using optical tweezers, micropipette aspiration and advanced confocal microscopy, combined with UV microablation.

Actin bundle deformation

Optical tweezer based stiffness measurement of actin bundles (F. Rueckerl, collaboration C. Sykes).