Session Q7: Mechanics in Cell Biology

Elastic Deformations During Bacterial Cell Growth

The wide variety of shapes and sizes found in bacterial species is almost universally defined by the cell wall, which is a cross-linked network of the material peptidoglycan. In recent years, cell shape has been shown to play a critical role in regulating many important biological functions including attachment, dispersal, motility, polar differentiation, predation, and cellular differentiation. In previous work, we have shown that the spatial organization of the peptidoglycan network can change the mechanical equilibrium of the cell wall and result in changes in cell shape. However, experimental data on the mechanical properties of peptidoglycan is currently limited. Here, we describe a straightforward, inexpensive approach for extracting the mechanical properties of bacterial cells in gels of user-defined stiffness, using only optical microscopy to match growth kinetics to the predictions of a continuum model of cell growth. Using this simple yet general methodology, we have measured the Young's modulus for bacteria ranging across a wide variety of shapes, sizes, and cell wall thicknesses, and our method can easily be extended to other commonly studied bacteria. This method makes it possible to rapidly determine how changes in genotype and biochemistry affect the mechanical properties of the cell wall, and may be particularly relevant for studying the relationship between cell shape and structure, the genetic and molecular control of the mechanical properties of the cell wall, and the identification of antibiotics and other small molecules that affect and specifically modify the mechanical properties of the cell wall. Our work also suggests that bacteria may utilize peptidoglycan synthesis to transduce mechanosensory signals from local environment.   

Mechanical influences in bacterial morphogenesis and cell division

Bacterial cells utilize a ring-like organelle (the Z-ring) to accomplish cell division. The Z-ring actively generates a contractile force and influences cell wall growth. We will discuss a general model of bacterial morphogenesis where mechanical forces are coupled to the growth dynamics of the cell wall. The model suggests a physical mechanism that determines the shapes of bacteria cells. The roles of several bacterial cytoskeletal proteins and the Z-ring are discussed. We will also explore molecular mechanisms of force generation by the Z-ring and how cells can generate mechanical forces without molecular motors.   

Matrix elasticity directs stem cell lineage specification

Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton~pulls on matrix~through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. \\[4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).\\[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).\\[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).\\[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).   

Shape and dynamics of tip growing cells

Walled cells have the ability to remodel their shape while sustaining an internal turgor pressure that can reach many atmospheres. I will describe how we may treat a tip growing cell as an osmotic engine which elongates via the assembly and expansion of cell wall in the apical region of the cell. A simple model that couples transport to growth allows us to determine the radius of the pollen tube and its growth velocity in terms of the turgor pressure and the secretion rate and rheology of the cell wall material, and results in simple scaling laws for the geometry and dynamics of the cell. We find that a single dimensionless parameter, which characterizes the relative roles of cell wall assembly and expansion, is sufficient to explain the observed variability in pollen tube shapes and also provides a framework for the comparative study of pollen tubes and fungal hyphae in an evolutionary context.   

Shape determination in motile cells

Flat, simple shaped, rapidly gliding fish keratocyte cell is the model system of choice to study cell motility. The cell motile appendage, lamellipod, has a characteristic bent-rectangular shape. Recent experiments showed that the lamellipodial geometry is tightly correlated with cell speed and with actin dynamics. These quantitative data combined with computational modeling suggest that a model for robust actin treadmill inside the 'unstretchable membrane bag'. According to this model, a force balance between membrane tension and growing and pushing actin network distributed unevenly along the cell periphery can explain the cell shape and motility. However, when adhesion of the cell to the surface weakens, the actin dynamics become less regular, and myosin-powered contraction starts playing crucial role in stabilizing the cell shape. I will illustrate how the combination of theoretical and experimental approaches helped to unravel the keratocyte motile behavior.