Biology subjects

Lalitha Sridhar, S.

Publications and source records attributed to Lalitha Sridhar, S..

3 recordsLinked to original sources

bioRxiv2021

Enhanced diffusion by reversible binding to active polymers

Cells are known to use reversible binding to active biopolymer networks to allow diffusive transport of particles in an otherwise impenetrable mesh. We here determine the motion of a particle that experiences random forces during binding and unbinding events while being constrained by attached polymers. Using Monte-Carlo simulations and a statistical mechanics model, we find that enhanced diffusion is possible with active polymers. However, this is possible only under optimum conditions that has to do with the relative length of the chains to that of the plate. For example, in systems where the plate is shorter than the chains, diffusion is maximum when many chains have the potential to bind but few remain bound at any one time. Interestingly, if the chains are shorter than the plate, we find that diffusion is maximized when more active chains remain transiently bound. The model provides insight into these findings by elucidating the mechanisms for binding-mediated diffusion in biology and design rules for macromolecular transport in transient synthetic polymers. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/428690v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1f09992org.highwire.dtl.DTLVardef@f26b4borg.highwire.dtl.DTLVardef@162368corg.highwire.dtl.DTLVardef@eb2b45_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2020

Percolation of Microparticle Matrix Promotes Cell Migration and Integration while Supporting Native Tissue Architecture

Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue-specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, we developed a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed tissue clay, that can be molded and crosslinked to mimic native tissue architecture. We utilized hyaluronic acid-based hydrogels, amorphously packed with acellular articular cartilage tissue particulated to ~125-250 microns in diameter and defined a percolation threshold of 0.57 (v/v) beyond which the compressive modulus exceeded 300kPa. Remarkably, primary chondrocytes recellularized particles within 48 hours, a process driven by chemotaxis, exhibited distributed cellularity in large engineered composites, and expressed genes consistent with native cartilage repair. We additionally demonstrated broad utility of tissue clays through recellularization and persistence of muscle, skin, and cartilage composites in a subcutaneous in vivo mouse model. Our findings suggest optimal strategies and material architectures to balance concurrent demands for large-scale mechanical properties while also supporting integration of dense musculoskeletal and connective tissues.

bioengineering↗

bioRxiv2018

A Statistical Model of Cell Wall Dynamics during Expansive Growth

Expansive growth is a process by which walled cells found in plants, algae and fungi, use turgor pressure to mediate irreversible wall deformation and regulate their shape and volume. The molecular structure of the primary cell wall must therefore be able to perform multiple function simultaneously such as providing structural support by a combining elastic and irreversible deformation and facilitate the deposition of new material during growth. This is accomplished by a network of microfibrils and tethers composed of complex polysaccharides and proteins that are able to dynamically mediate the network topology via constant detachment and reattachment events. Global biophysical models such as those of Lockhart and Ortega have provided crucial macroscopic understanding of the expansive growth process, but they lack the connection to molecular processes that trigger network rearrangements in the wall. In this context, we propose a statistical approach that describes the population behavior of tethers that have elastic properties and the ability to break and re-form in time. Tether properties such as bond lifetimes and stiffness, are then shown to govern global cell wall mechanics such as creep and stress relaxation. The model predictions are compared with experiments of stress relaxation and turgor pressure step-up from existing literature, for the growing cells of incised pea (Pisum sativus L.), algae Chara corallina and the sporangiophores of the fungus, Phycomyces blakesleeanus. The molecular parameters are estimated from fits to experimental measurements combined with the information on the dimensionless number {Pi}pe that is unique to each species. To our knowledge, this research is the first attempt to use a statistical approach to model the cell wall during expansive growth and we believe it will provide a better understanding of the cell wall dynamics at a molecular level.

biophysics↗