Browsing by Author "Feng, Jingchen"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Alignment and nonlinear elasticity in biopolymer gels
    (American Physical Society, 2015) Feng, Jingchen; Levine, Herbert; Mao, Xiaoming; Sander, Leonard M.; Center for Theoretical Biological Physics
    We present a Landau-type theory for the nonlinear elasticity of biopolymer gels with a part of the order parameter describing induced nematic order of fibers in the gel. We attribute the nonlinear elastic behavior of these materials to fiber alignment induced by strain. We suggest an application to contact guidance of cell motility in tissue. We compare our theory to simulation of a disordered lattice model for biopolymers. We treat homogeneous deformations such as simple shear, hydrostatic expansion, and simple extension, and obtain good agreement between theory and simulation. We also consider a localized perturbation which is a simple model for a contracting cell in a medium.
  • Thumbnail Image
    Item
    Mechanical Interaction between Cells and Extra Cellular Matrix
    (2016-08-29) Feng, Jingchen; Levine, Herbert
    The mechanical interactions between Cells and Extracellular Matrix (ECM) play a central role in various cellular processes including motility, differentiation, shape change and wound healing. Contracting cells actively pull the surrounding ECM and cause its remodeling. At the same time, the remodeled ECM in turn regulates both cell mechanical behavior and gene expression. To understand ECM remodeling and its impact on cell regulation, we first construct two continuum theories, a Landau-type theory and a scaling law-type theory, to understand the nonlinear elasticity of ECM. The former elucidates the relation between fiber alignment and nonlinear elasticity, while the later generalizes previous scaling laws and reveals new mechanical regimes in the phase diagram. Next, we build an elastic model, which explicitly includes both cells and collagen fibers, to explore the micromechanics of cellularized ECM on the scale of cell size. It shows that contracting cells remodel the micromechanics of their surrounding ECM in a strain and distance-dependent manner. Finally, we introduce the viscoelastic feature into this model and show viscoelasticity is essential in ECM remodeling. This work provides a platform to study Cell-ECM interactions regulated cell motility and it potentially serves as a guide for experimental work.
  • Thumbnail Image
    Item
    Modeling delayed processes in biological systems
    (American Physical Society, 2016) Feng, Jingchen; Sevier, Stuart A.; Huang, Bin; Jia, Dongya; Levine, Herbert; Center for Theoretical Biological Physics
    Delayed processes are ubiquitous in biological systems and are often characterized by delay differential equations (DDEs) and their extension to include stochastic effects. DDEs do not explicitly incorporate intermediate states associated with a delayed process but instead use an estimated average delay time. In an effort to examine the validity of this approach, we study systems with significant delays by explicitly incorporating intermediate steps. We show that such explicit models often yield significantly different equilibrium distributions and transition times as compared to DDEs with deterministic delay values. Additionally, different explicit models with qualitatively different dynamics can give rise to the same DDEs revealing important ambiguities. We also show that DDE-based predictions of oscillatory behavior may fail for the corresponding explicit model.
  • Thumbnail Image
    Item
    Phenomenological modeling of durotaxis
    (American Physical Society, 2017) Yu, Guangyuan; Feng, Jingchen; Man, Haoran; Levine, Herbert
    Cells exhibit qualitatively different behaviors on substrates with different rigidities. The fact that cells are more polarized on the stiffer substrate motivates us to construct a two-dimensional cell with the distribution of focal adhesions dependent on substrate rigidities. This distribution affects the forces exerted by the cell and thereby determines its motion. Our model reproduces the experimental observation that the persistence time is higher on the stiffer substrate. This stiffness-dependent persistence will lead to durotaxis, the preference in moving towards stiffer substrates. This propensity is characterized by the durotaxis index first defined in experiments. We derive and validate a two-dimensional corresponding Fokker-Planck equation associated with our model. Our approach highlights the possible role of the focal adhesion arrangement in durotaxis.
  • Thumbnail Image
    Item
    RACIPE: a computational tool for modeling gene regulatory circuits using randomization
    (Springer Nature, 2018) Huang, Bin; Jia, Dongya; Feng, Jingchen; Levine, Herbert; Onuchic, José Nelson; Lu, Mingyang; Center for Theoretical Biological Physics
    BACKGROUND: One of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, especially for large networks. RESULTS: We present a user-friendly computational tool for the community to use our newly developed method named random circuit perturbation (RACIPE), to explore the robust dynamical features of gene regulatory circuits without the requirement of detailed kinetic parameters. Taking the network topology as the only input, RACIPE generates an ensemble of circuit models with distinct randomized parameters and uniquely identifies robust dynamical properties by statistical analysis. Here, we discuss the implementation of the software and the statistical analysis methods of RACIPE-generated data to identify robust gene expression patterns and the functions of genes and regulatory links. Finally, we apply the tool on coupled toggle-switch circuits and a published circuit of B-lymphopoiesis. CONCLUSIONS: We expect our new computational tool to contribute to a more comprehensive and unbiased understanding of mechanisms underlying gene regulatory networks. RACIPE is a free open source software distributed under (Apache 2.0) license and can be downloaded from GitHub ( https://github.com/simonhb1990/RACIPE-1.0 ).
  • Thumbnail Image
    Item
    Stress-induced plasticity of dynamic collagen networks
    (Springer Nature, 2017) Kim, Jihan; Feng, Jingchen; Jones, Christopher A.R.; Mao, Xiaoming; Sander, Leonard M.; Levine, Herbert; Sun, Bo
    The structure and mechanics of tissues is constantly perturbed by endogenous forces originated from cells, and at the same time regulate many important cellular functions such as migration, differentiation, and growth. Here we show that 3D collagen gels, major components of connective tissues and extracellular matrix (ECM), are significantly and irreversibly remodeled by cellular traction forces, as well as by macroscopic strains. To understand this ECM plasticity, we develop a computational model that takes into account the sliding and merging of ECM fibers. We have confirmed the model predictions with experiment. Our results suggest the profound impacts of cellular traction forces on their host ECM during development and cancer progression, and suggest indirect mechanical channels of cell-cell communications in 3D fibrous matrices.