A5016918922- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Gene Regulatory Network Analysis
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Advanced biosensing and bioanalysis techniques
- Force Microscopy Techniques and Applications
- Microtubule and mitosis dynamics
- Material Dynamics and Properties
- Nanopore and Nanochannel Transport Studies
- Cellular transport and secretion
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Axon Guidance and Neuronal Signaling
- Biocrusts and Microbial Ecology
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Toxoplasma gondii Research Studies
- Hippo pathway signaling and YAP/TAZ
- Stochastic processes and statistical mechanics
- Blood properties and coagulation
- Fungal and yeast genetics research
- RNA Interference and Gene Delivery
- Bacterial Genetics and Biotechnology
- Pickering emulsions and particle stabilization
University of Tennessee at Knoxville
2016-2025
Knoxville College
2015-2020
National Institute for Mathematical and Biological Synthesis
2016-2019
University of California, San Francisco
2019
Massachusetts Institute of Technology
2012-2014
Division of Chemistry
2013
Stanford University
2009
Activation of the small guanosine triphosphatase H-Ras by exchange factor Son Sevenless (SOS) is an important hub for signal transduction. Multiple layers regulation, through protein and membrane interactions, govern activity SOS. We characterized specific individual SOS molecules catalyzing nucleotide in H-Ras. Single-molecule kinetic traces revealed that samples a broad distribution turnover rates stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional...
Immune cells have intensely physical lifestyles characterized by structural plasticity and force exertion. To investigate whether specific immune functions require stereotyped mechanical outputs, we used super-resolution traction microscopy to compare the synapses formed cytotoxic T with contacts other cell subsets macrophages. were globally compressive, which was fundamentally different from pulling pinching associated macrophage phagocytosis. Spectral decomposition of exertion patterns...
Misregulation of the signaling axis formed by receptor tyrosine kinase (RTK) EphA2 and its ligand, ephrinA1, causes aberrant cell-cell contacts that contribute to metastasis. Solid tumors are characterized an acidic extracellular medium. We intend take advantage this tumor feature design new molecules specifically target tumors. created a novel pH-dependent transmembrane peptide, TYPE7, altering sequence domain EphA2. TYPE7 is highly soluble interacts with surface lipid membranes at neutral...
Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes to gene expression. Yet, little is known about how expression bursting—the episodic process mRNA proteins are produced bursts. Here, we simultaneously measured protein...
Many key biochemical reactions that mediate signal transduction in cells occur at the cell membrane, yet how two-dimensional membrane environment influences collective behavior of signaling networks is poorly understood. We study models two topologically different pathways exhibit bistability, examining effects reduced protein mobility and increased concentration as well due to differences spatiotemporal correlations between three-dimensional cytoplasm. The model represent distributive...
Recent work has demonstrated that nonstimulatory endogenous peptides can enhance T cell recognition of antigen, but MHCI- and MHCII-restricted systems have generated very different results. TCRs need to interact with the peptide–MHC (pMHC), showing peptide specificity for activation enhancers or coagonists. In contrast, MHCI-restricted cells studied date show no such coagonists, suggesting CD8 binding noncognate MHCI is more important. Here we how this dichotomy be resolved by varying TCR...
ABSTRACT Immune cells live intensely physical lifestyles characterized by structural plasticity, mechanosensitivity, and force exertion. Whether specific immune functions require stereotyped patterns of mechanical output, however, is largely unknown. To address this question, we used super-resolution traction microscopy to compare cytotoxic T cell synapses with contacts formed other subsets macrophages. were globally locally protrusive, which was fundamentally different from the coupled...
Molecular motors facilitate intracellular transport through a combination of passive motion in the cytoplasm and active along cytoskeletal filaments. Although on individual filaments is often well characterized, it remains challenge to understand their networks Here we use computer simulations stochastic jump process determine first-passage times (FPTs) molecular motor traversing an interval containing randomly distributed fixed length. We characterize mean time (MFPT) as function number...
The adsorption of particles onto fluid membranes can lead to membrane-mediated interactions between that promote their self-assembly and changes in membrane morphology. However, contrast with rigid particles, relatively little is known about deformable which introduce additional complexities due the mutual deformability membrane. Here, we use Monte Carlo simulations umbrella sampling investigate equilibrium properties hinge-like adsorbed on vesicles by means anisotropic, attractive...
The organization of cytoskeletal elements is pivotal for coordinating intracellular transport in eukaryotic cells. Several quantitative measures based on image analysis have been proposed to characterize morphometric features fluorescently labeled actin networks. While helpful detecting differences between treatments or genotypes, the accuracy these could not be rigorously assessed due a lack ground-truth data which they compared. To overcome this limitation, we utilized coarse-grained...
The adsorption of polymers onto fluid membranes is a problem fundamental interest in biology and soft materials, part because the flexibility can lead to nontrivial coupling between polymer membrane configurations. Here, we use Monte Carlo computer simulations study semiflexible vesicle. Polymer significantly impact both vesicle shapes, identify distinct classes configurations that emerge as function persistence length, bending rigidity, strength, size. Large-scale deformations include...
During cytokinesis, fission yeast coordinates actomyosin ring constriction with septum ingression, resulting in concentric furrow formation by a poorly defined mechanism. We report that cells lacking the Cdc42 activator Gef1, combined an activated allele of formin, Cdc12, display non-concentric furrowing. Non-concentrically furrowing uneven distribution scaffold Cdc15 along ring. This suggests after assembly, uniform enables proper formation. find assembly is recruited to Arp2/3...
Crowding leads to enhanced interactions between ring polymers and promotes adsorption of surfaces.
Cell-free protein synthesis is an important tool for studying gene expression and harnessing it applications. In cells, regulated in part by the spatial organization of transcription translation. Unfortunately, current cell-free approaches are unable to control molecular components needed expression, which limits ability probe utilize its effects. Here, we show, using complementary computational experimental approaches, that macromolecular crowding can be used translational efficiency...
We use Monte Carlo computer simulations to investigate tubular membrane structures with and without semiflexible polymers confined inside. At small values of bending rigidity, empty fluid non-fluid tubes exhibit markedly different behavior, membranes adopting irregular, highly fluctuating shapes maintaining extended tube-like structures. Fluid membranes, unlike a local maximum in specific heat as their rigidity increases. The peak is coincident transition further find that confining polymer...
Macromolecular crowding is a feature of cellular and cell-free systems that, through depletion effects, can impact the interactions semiflexible biopolymers with surfaces. In this work, we use computer simulations to study crowding-induced adsorption polymers on otherwise repulsive Crowding particles are modeled explicitly, investigate interplay between bending stiffness polymer volume fraction size particles. Adsorption flat surfaces promoted by stiffer polymers, smaller particles, larger...
Most models for ethylene signaling involve a linear pathway. However, measurements of seedling growth kinetics when is applied and removed have resulted in more complex network that include coherent feedforward, negative feedback, positive feedback motifs. The dynamical responses the proposed networks not been explored quantitative manner. Here, we explore (i) whether any are capable producing growth-response behaviors consistent with experimental observations (ii) what mechanistic roles...
T-cells use microvilli to search the surfaces of antigen-presenting cells for antigenic ligands. The active motion scanning provides a force-generating mechanism that is intriguing in light single-molecule experiments showing applied forces increase lifetimes stimulatory receptor–ligand bonds (catch-bond behavior). In this work, we introduce theoretical framework explore microvillar tip above an surface when receptors on stochastically bind ligands and dissociate from them force-dependent...
Adsorption of nanoparticles on a membrane can give rise to interactions between particles, mediated by deformations, that play an important role in self-assembly and remodeling. Previous theoretical experimental research has focused with fixed shapes, such as spherical, rod-like, curved nanoparticles. Recently, hinge-like DNA origami nanostructures have been designed tunable mechanical properties. Inspired this, we investigate the equilibrium properties particles adsorbed elastic using Monte...
The one-dimensional, single-occupancy lattice gas exhibits highly cooperative particle motion and provides an interesting challenge for theoretical methods designed to describe caging in liquids. We employ this model effort gain insight into phenomena more realistic models of liquids, using a diagrammatic kinetic theory density fluctuations develop series approximations the equations van Hove self-correlation function. are formulated terms irreducible memory function, we assess their...
Positive feedback is a common feature in signal transduction networks and can lead to phenomena such as bistability propagation by domain growth. Physical features of the cellular environment, spatial confinement mobility proteins, play important but inadequately understood roles shaping behavior signaling networks. Here, we use stochastic, spatially resolved kinetic Monte Carlo simulations explore positive network function system size, shape, molecules. We show that these physical...
Nanoparticles adsorbed on a membrane can induce deformations of the that give rise to effective interactions between particles. Previous studies have focused primarily rigid nanoparticles with fixed shapes. However, DNA origami technology has enabled creation deformable nanostructures controllable shapes and mechanical properties, presenting new opportunities modulate particles surfaces. Here we use coarse-grained molecular dynamics simulations investigate deformable, hinge-like anchored...