Biophysical Modelling

Superresolution microscopy reveals distinct localisation of full length IRSp53 and its I-BAR domain protein within filopodia

Published date : 21 Feb 2019

Superresolution microscopy offers the advantage of imaging biological structures within cells at the nano-scale. Here we apply two superresolution microscopy techniques, specifically 3D structured illumination microscopy (3D-SIM) and direct stochastic optical reconstruction microscopy (dSTORM), a type of single molecule localisation microscopy, to localise IRSp53 protein and its I-BAR domain in relation to F-actin within filopodia. IRSp53 generates dynamic (extending and retracting) filopodia 300 nm wide with a distinct gap between IRSp53 and F-actin.

type
Journal Paper
journal
Scientific Reports 9, Article no: 2524(2019). doi: 10.1038/s41598-019-38851-w
Impact Factor
4.122

Anisotropic traction stresses and focal adhesion polarization mediates topography-induced cell elongation

Published date : 30 Jul 2018

Cell elongation and differentiation has been shown to be modulated by topographical cues provided by grating substratum. However, little is known about the mechanisms and forces involved in the grating-induced cell elongation, due to the difficulty in fabricating soft elastic gels that allow 3-dimensional (3D) cell traction stress measurements. In this paper, we present a method to fabricate soft elastic polyacrylamide grating substrates, using an imprinted polyethylene terephthalate mould, for 3D cell traction stress measurements.

type
Journal Paper
journal
Biomaterials, Vol. 181, October 2018, Pg 103-112, doi: 10.1016/j.biomaterials.2018.07.057
Impact Factor
8.806

Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns

Published date : 22 Jun 2018

Endothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical Delta-Notch models produce a spatial pattern of tip cells separated by a single stalk cell, or the salt-and-pepper pattern. However, classical models cannot explain alternative tip-stalk patterning, such as tip cells that are separated by two or more stalk cells.

type
Journal Paper
journal
Scientific Reports 8, No. 9519, 2018, doi: 10.1038/s41598-018-27645-1
Impact Factor
4.122

Three-dimensional computational model of multiphase flow driven by a bed of active cilia

Published date : 02 May 2018

Micro-scale physiological fluid propulsion is often accomplished with arrays of beating cilia. It is well-known that cilia can spontaneously coordinate their beat patterns to form metachronal waves. While it is generally agreed upon that metachronal waves arise largely due to hydrodynamic coupling, their effects on fluid propulsion are not thoroughly explored. There are presently complex, nonlinear models where cilia motion mimics their internal mechanisms; however these models are often computationally challenging and expensive to perform.

type
Journal Paper
journal
Computers & Fluids, Vol. 170, 15 Jul 2018, Pg 222-235, doi: 10.1016/j.compfluid.2018.05.001
Impact Factor
2.221

Human mesenchymal stem cell basal membrane bending on gratings is dependent on both grating width and curvature

Published date : 24 Apr 2018

The topography of the extracellular substrate provides physical cues to elicit specific downstream biophysical and biochemical effects in cells. An example of such a topographical substrate is periodic gratings, where the dimensions of the periodic gratings influence cell morphology and directs cell differentiation.

type
Journal Paper
journal
Scintific Reports 8, No. 6444, 2018, doi: 10.1038/s41598-018-24123-6
Impact Factor
4.122

A computational model for how cells choose temporal or spatial sensing during chemotaxis

Published date : 05 Mar 2018

Cell size is thought to play an important role in choosing between temporal and spatial sensing in chemotaxis. Large cells are thought to use spatial sensing due to large chemical difference at its ends whereas small cells are incapable of spatial sensing due to rapid homogenization of proteins within the cell. However, small cells have been found to polarize and large cells like sperm cells undergo temporal sensing. Thus, it remains an open question what exactly governs spatial versus temporal sensing.

type
Journal Paper
journal
PLOS Computational Biology, 2018, 14(3), doi: 10.1371/journal.pcbi.1005966
Impact Factor
4.542

Cell-Cell Adhesion and Cortical Actin Bending Govern Cell Elongation on Negatively Curved Substrates

Published date : 20 Feb 2018

Physiologically, cells experience and respond to a variety of mechanical stimuli such as rigidity and topography of the extracellular matrix. However, little is known about the effects of substrate curvature on cell behavior. We developed a novel, to our knowledge, method to fabricate cell culture substrates with semicylindrical grooves of negative curvatures (radius of curvature, Rc = 20-100 μm). We found that negative substrate curvatures induced elongation of mesenchymal and epithelial cells along the cylinder axis.

type
Journal Paper
journal
Biophysical Journal 114, Pg 1707-1717, April 10, 2018 doi: 10.1016/j.bpj.2018.02.027
Impact Factor
3.495

Structural analyses unravel the molecular mechanism of cyclic di-GMP regulation of bacterial chemotaxis via a PilZ adaptor protein

Published date : 16 Nov 2017

The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility, and pathogenicity. c-di-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism for PilZ protein–mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ cocrystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa.

type
Journal Paper
journal
Journal of Biological Chemistry, 5 January 2018, 293, 1, 100-111
Impact Factor
4.125

The role of apical contractility in determining cell morphology in multilayered epithelial sheets and tubes

Published date : 19 Jun 2017

A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar.

type
Journal Paper
journal
Physical Biology, Vol. 14, No. 4, 2017, doi: 10.1088/1478-3975/aa7afc
Impact Factor
1.837

Comparison of cellular oscillations driven by noise or deterministic mechanisms under cell-size scaling

Published date : 28 Oct 2016

Ultradian cycles are frequently observed in biological systems. They serve important roles in regulating, for example, cell fate and the development of the organism. Many mathematical models have been developed to analyze their behavior. Generally, these models can be classified into two classes: Deterministic models that generate oscillatory behavior by incorporating time delays or Hopf bifurcations, and stochastic models that generate oscillatory behavior by noise driven resonance. However, it is still unclear which of these two mechanisms applies to cellular oscillations.

type
Journal Paper
journal
Physical Review E, 2016 Oct;94(4-1), doi: https://doi.org/10.1103/PhysRevE.94.042425
Impact Factor
2.366