Session K2: Biological and Soft Condensed Matter Physics II

Modeling Active Microtubule-motor Networks

Cell division of one cell into two daughter cells is necessary for organisms to grow or reproduce. Segregation of the genetic material into the daughter cells during cell division is performed by a molecular machine called the mitotic spindle that exerts forces on chromosomes and moves them to the correct locations during cell division. The mitotic spindle is a nonequilibrium structure composed of filaments called microtubules and motor proteins that bundle and slide the filaments. The mitotic spindle is inspiring new work in which components of the mitotic spindle are taken outside of cells to make new types of biologically-inspired active materials. To improve our understanding of these active materials, we are studying course-grained models of liquid-crystalline filaments (microtubules) driven by active crosslinks (motors). This model is investigated using a combination of Brownian dynamics and kinetic Monte Carlo simulation. We observed novel states of the system, including bundles and sheets, active nematic phases, and laning.\\[4pt] In collaboration with Robert Blackwell and Matthew Glaser, University of Colorado - Boulder.   

Proteome and cell biophysics on the back of an envelope

We investigate the heterogeneity of several biophysical properties across the proteome, the entire set of proteins inside a cell. The global approach adopted here, in stark contrast to the traditional approach of one-protein-at-a-time, offers us insights to several foundational questions: 1) Why are cells so sensitive to temperature changes? How can the cell's maximum growth temperature be so close to the cell-death temperature? 2) What makes thermophiles withstand high temperature? 3) Why are cells so crowded? 4) What are the competitions between different physical processes inside a cell and their relative importance and evolutionary implications? Predictions are made using existing experimental data, protein knowledge bases, detailed simulations and simple theoretical calculations.   

Modeling stochastic cell dynamics with adhesion anisotropy quantitatively reproduces convergent extension

Epithelial cells in {\it Drosophila} embryos intercalate together during germ-band extension in order to elongate the entire embryo along the anterior-posterior axis, a process more broadly known as convergent extension. {\it In silico} simulation of hexagonal cell matrices provides an inexpensive way to test the validity of possible mechanisms governing convergent extension of epithelial tissues. Our proposed system is node-based as opposed to pixel-based, storing data only for the node points defining the idealized polygons representing individual cells. This brings simulation times down from days to hours. Using Monte Carlo simulation techniques, the energy function used takes into account cell volume and membrane conservation as well as adhesion between surrounding cells. Our model takes a passive adhesion approach by assuming planar polarized distributions of adhesiveness within the cell. This leads to convergent extension using only Brownian motion. This adhesion-based model also allows us to add in a level of heterogeneity, where cell polarizations don't align perfectly along the dorsal-ventral axis due to a mistake in cellular machinery. This results in longer monopolar adhesions along interfaces, leading to slower interface contraction and complex cell behaviors.   

Weakening the Cell Elasticity of Chlorella Vulgaris under Nitrate Starvation

\textit{Chlorella vulgaris} is a unicellular, photosynthetic green alga. This strain of Chlorella is capable of producing high lipid content---up to 50{\%} of its dry biomass when experiencing severe nutrient stress. The strength of the cell wall influences the susceptibility of the cells to rupture and is hypothesized to be related to extractability of the lipids. Upon nutrient deprivation, algal cells increase lipid content but concurrently a reduction in extraction efficiency has been observed. To study algal cell wall elasticity, Chlorella cells were grown in replete medium, which over time became deplete in nitrate and other nutrients. Samples were harvested at three distinct time points. Through Atomic Force Microscope (AFM) measurements, we obtained force vs distance data as the AFM probe tip is brought in contact with an immobilized cell, thus deforming its surface. The Hertz model for membrane deformation, modified to account for AFM probe shape, is used to fit to the quadratic curve from the force curve measurements. By fitting the model to the data, the Young's Modulus for the cell can be extracted. Analysis of the data leads to the conclusion that nitrate deprivation results in a decreased Young's Modulus of the cell.   

Expanding the locomotion repertoire of the eigenfish: Study of wildtype and mutant zebrafish larvae escape response

The zebrafish larva is a thoroughly studied and an extensively used model for behavioral and biomedical research. The Zebrafish Laboratory at the University of Illinois at Urbana-Champaign has applied a mathematical method to describe quantitatively the larva's swimming behavior. By this method, 98{\%} of the complex locomotion of the free swimming behavior of the larva was described using three main components, or three ``\textit{eigen}fish.'' Our focus is on the quantification of a different swimming behavior called escape response in wildtype (WT) and the Space Cadet (SPC) mutant zebrafish larvae. Although more data is required before assuming certainty in our results, the escape response of both WT and SPC larva was also described up to 98{\%} by three eigenfish. However, the eigenfish for the SPC mutant and the wildtype varied from each other.