Mentor: Professor Guy Genin
Both plant and animal cells have at their periphery a relatively thin layer of a molecule that has sticky carbohydrates attached to a protein backbone. These molecules, called proteoglycans in animals and arabinogalactans inplants, shifted from solid-like to fluid-like based upon the electrochemical environment, with monovalent cations screening out stickiness and divalent cations cross-linking carbohydrates. Understanding the regulation of these molecules may provide new insight into how both plant and animal cells can adapt their microenvironment and subsequent function in response to stress.
The student will work to unify our understanding of how plant and animal cells can stably manipulate proteoglycan-like molecules. We developed a computational model that predicts how proteoglycan and arabinogalactan mechanics change in response to the action of proton and calcium pumps in the cell membrane. The student will track via atomic force microscopy the mechanical responses of isolated arabinogalactans in varying ionic concentrations, and evaluate how structures such as trichomes alter their mechanics via pH changes once probed mechanically (Fig. 1). Such integrated models and experiments may uncover critical dynamics permanent, mechanically induced changes to the cell microenvironment.
Mentor: Professor Hani Suleiman
The answer to this question is that they usually do not, and chronic kidney disease thus has no cure. However, results in our lab using a new in vitro testing platform suggest that in certain cases, healing kidney cells can adopt muscle-like structures that help them template out new slit diaphragms and restore kidney function.
The student will use this new culture platform to test the hypothesis that mechanical memory inserted into these cells during mechanical loading governs the fate and disposition of these structures, thereby laying the groundwork for future interventions that apply mechanical cues to guide healing in chronic kidney disease.
Mentor: Professor Marcus Foston
Cellulose nanocrystal (CNC) is a highly crystalline derivative of lignocellulosic and cellulosic biomasses. This material poses extensive applications due to its availability, high surface area to volume ratio, biodegradability, and mechanical properties, including its use as a reinforcement material in protein nanocomposites. Due to the anisotropic property and random orientation of CNC in common filler matrix system, CNC-based nanocomposite has great potential of reinforcement in mechanical properties. Our project focuses on understanding CNC-based protein nanocomposite by aligning CNC orientations in nanocomposites using magnetic fields, specifically magnetic resonance imaging (MRI) in WashU medical campus to further enhance the mechanical properties. Different characterizations are used, including different composition analysis, mechanical testing and imaging.
The student will synthesize CNC based protein nanocomposites with magnetic alignment, and understand the filler matrix interactions in nanocomposite system. Results will test the hypothesis that magnetically aligned CNC based nanocomposites will show great enhancement of mechanical strength and properties compared with no alignment of CNC. Organic chemistry background is strongly recommended. Experience in undergraduate chemistry lab would be useful but not required.
Mentor: Professor Ram Dixit
The spectacular diversity of cell shapes in both plants and animals is driven by nanoscale protein polymers called microtubules. The Dixit lab studies how, in plants, microtubules drive cell shape by organizing the relatively rigid cell wall. This orchestration of wall formation by microtubule arrays supports a hypothesis that deformation of the microtubule array can be remembered by a cell by becoming locked into the cell wall.
The student will characterize cell wall properties of a special mutant of the model plant Arabidopsis thaliana that grows in a twisted fashion and has mutations to the microtubule cytoskeleton. The goal is to determine whether this twisted phenotype arises due to specific changes in the composition of the wall, or due to memory of the twisted microtubule pattern. The student would learn plant work, protein purification and fluorescence microscopy, plus gain experience with integrating different data sets to address a research question. The student would conduct monosaccharide and FTIR analyses to determine cell wall composition of the stems, and conduct rheological experiments to determine the mechanical properties of these stems. The student would also perform live imaging of microtubules in these mutants to determine if changes in microtubule dynamics and organization correlate to altered cell wall and growth properties.
Mentor: Professor Amit Pathak
During organ development and progression of diseases such as metastatic cancer, cells migrate both singly and collectively on matrices of varying stiffness. We study how grouped cells remember matrices and use stored information to navigate matrices with heterogeneous topography and confinement.
The student will fabricate hydrogels of at least two different stiffnesses using our technologies and perform experiments involving collective cell migration on these using breast epithelial cells and mutant cells. By analyzing time-lapse and confocal microscopy data in the = context of our simplified mathematical models, the student will seek to understand the spatiotemporal variation of migration and mechanotransduction markers. Experiments will show how mutants within a healthy cell population can dominate collective memory in migration.
Mentor: Professor Jessica Wagenseil
Elastic fibers are critical for elastic recoil in the large arteries during the cardiac cycle. Elastic fiber assembly can be compromised and elastic fiber degradation can be expedited in genetic and acquired vascular disease, compromising arterial function.
The student will perform studies to determine whether or not specific reagents can increase elastic fiber assembly and/or prevent elastic fiber degradation. Methods include biochemistry, cell culture, microscopy, and in vitro mechanical testing of mouse aorta.
Mentor: Professor Nathaniel Huebsch
The Huebsch lab focuses on understanding why inherited mutations in contractile proteins of cardiomyocytes lead to electrical conduction abnormalities, which ultimately lead to sudden death in children. We hypothesize that mutations in contractile proteins within the sarcomere alter cardiomyocyte calcium and voltage handling, and that changes in the mechanics of the tissue environment will exacerbate this response.
The student will work with Huebsch lab team members to form arrays of cardiac micro-tissues derived from human induced pluripotent stem cells, perform high speed video microscopy of the tissues and use Matlab coding routines to convert these videos into information on tissue-level contractility, voltage and calcium handling. He/she will also assist in structural and biochemical analysis of the tissues and gain proficiency in these techniques.