A computational and physical perspective of molecules and the cell has changed the biochemical focus of biology. Mechanobiology studies the role of forces in the structure and function of molecules, cells, and tissues. This new view relies on structure, not only the traditional methods of x-ray crystallography and NMR spectroscopy but also structures from imaging by light and electron microscopy. The resulting mechanical and 3D models rely on powerful computational biology algorithms and approaches.
New and powerful imaging methods are being developed and applied to capture dynamics – from molecules to tissues. Very stable AFM methods are able to measure small but significant forces in the folding and unfolding of proteins and DNA. The fluctuations in signal as a fluorescently marked protein or organelle passes through a beam of light can be transformed into an image of diffusion by Fluorescence Correlation Spectroscopy. The forces that drive the large-scale and coordinated migration of embryonic cells are being captured as strain maps of the developing zebrafish embryo through Hi-Lo DSLM.
to Centre for Bioimaging Sciences (CBIS) website
The foundation of mechanobiology is the biophysics of mechanics -the molecular and cellular forces which act to shape cells and tissues, where they function in a highly controlled manner. These forces act in concert with the microenvironment and through mechanical and chemical interactions between and among cells. Mechanobiology molds the architecture of the developing embryo, drives differentiation of stem cells to regenerate tissues in a healthy or diseased organ, and the powers metastasis of cancers. Biophysical Sciences faculty studies how gene expression is highly-controlled through mechanical feedbacks from the cell surface to the nucleus size and shape, the development of strain in the development of embryonic tissues, and how tension in epithelial sheets is generated by interactions with neighboring tissues – giving rise to gastrulation and other coordinated embryonic movements. Dynamics at the molecular and subcellular level are being investigated with highly sophisticated biophysical methods such as SPM/ Fluorescence Correlation Spectroscopy/Imaging, novel microfabricated formats for visualizing protein dynamics in the TEM or forming and visualizing in-plane cell-cell contacts, or super-resolution imaging methods to visualize large-scale tissue movements or micro-scale vesicle trafficking.
Mechanisms in biology are founded on structure and thus Structural Biology has expanded to include microscopy and imaging. At the atomic and molecular level, X-ray crystallographers and NMR spectroscopists are studying important structures and mechanisms such as RNAi holoenzyme complex and RNAi processing, bacterial secretion, signal transduction, and biosynthesis. New methods such as cryoEM and super-resolution microscopy enable exploration of cell biology structures such as the organization of chromatin and the structure of the flagellum and its associated structures in model algae and protozoan parasite systems.
Computation is a tool not only in the processing and analysis of data but also in the simulation of models to test our models. Experimental methods now generate more data than can be handled without computational methods, the biological questions are too complex to test before simulation as a computational or structural model. DBS faculty are at the forefront of computational analysis of biological structures and systems, modeling at the molecular to systems levels, mathematical methods to constrain biological models, and development of new algorithms and methods for dynamics and structures.