10 Dec 2010
Roland Eils
Integrative Bioinformatics and Systems Biology (iBioS)
University of Heidleberg, Germany
Mechanical properties of the cell nucleus play an important role in maintaining the integrity of the genome and controlling the cellular force balance. The structural integrity of the nuclear interior is required for the simultaneous performance of essential biochemical processes such as replication, transcription and splicing. The nuclear functional architecture depends on the material properties of the cell nucleus. Irregularities in these properties have been related to a variety of force-dependent processes in the cell, such as migration, division, growth or differentiation. Characterizing the mechanical properties of the cell nucleus in situ and relating these parameters to cellular phenotypes, molecular function or disease states remains a challenging task. Here, I will present the mathematical basis of a general framework for functional mechanical cellular phenotyping that allows the determination of material properties from volumetric cellular deformations measured by time-lapse fluorescence microscopy. Volumetric displacements are computed as a solution of an elastomechanic boundary value problem that depend on material properties, i.e., stiffness and compressibility. By minimizing the differences between measured cellular deformations and computationally predicted displacements we are able to predict essential material properties of cells. Beyond the mathematical basis of this framework I will show how this framework can be applied for efficiently probing the mechanical properties of cells on large scale by contactless optical stretching of cells. First results will be shown how we estimate mechanical properties of cells under functional perturbations by RNAi and chemical drugs interfering with the actin/myosin filaments, intermediate filaments and microtubules, respectively.