Pradeep Keshavanarayana (he/him)

• Computational mechanics

• Single cell mechanics

• Endothelial cells dynamics

• Mechanical/Numerical modelling

• Continuum mechanics

• Finite element methods

Cells are the fundamental units of living organisms controlling the behaviour of tissues, organs and thereby the organ system. The mechanical stimuli has been found to contribute towards changes in mechanical properties of cells, sometimes resulting in diseases. Focal adhesions present on the cell membrane contain mechanosensitive proteins called integrins which can form a connection between the cell and the extra cellular matrix, and thus sense the properties of the substrate and thereby the external stimuli. This creates  a chain of biochemical reactions within the cytoplasm, leading to a cross bridge between  the actin and myosin proteins in the presence of calcium ions, forming stress fibres. 

In this project, a novel DIY design of an uni-axial cell stretcher is developed and manufactured using  additive technology (3D printing). Experiments are performed on Fibroblast and Osteoblast cells. Results showed that cell reorient away from the direction of loading upon subjected to cyclic stretch. 

A numerical model was developed where in the stress fibre and focal adhesion growth models are extended and coupled through a feedback loop involving cytoplasmic calcium concentration. The effect of substrate stiffness on the response of cells is analysed. The mathematical model developed results in a coupled system of equations, for which the solution scheme needed special consideration. Noting the limitation on the time step that could be used with the staggered coupling scheme, a monolithic coupling scheme is developed where the system of equations are solved simultaneously. 

Endothelial cells form an inner lining of blood vessels, termed endothelium. They are responsible for regulating the movement of molecules through this layer, permeability, by controlling the dynamics of gaps between cells. Recent discoveries have shown that permeability of the endothelium is high in vascular diseases such as atherosclerosis and even in cancer. 

In this project, a continuum level FE model is being developed to understand the dynamics of endothelium when subjected to several loads simultaneously. A mechanics based approach is followed that can simulate the response of endothelium to varying physical and chemical properties of the surroundings. In addition to 2D simulations, the continuum framework allows studies in 3D as well. 

• P.Keshavanarayana, M.Ruess, R.de Borst. On the monolithic and staggered solution of cell contractility and focal adhesion growth, International Journal for Numerical Methods in Biomedical Engineering, 2018.    
  [ https://doi.org/10.1002/cnm.3138 ]

• P.Keshavanarayana, M.Ruess, R.de Borst. A feedback-loop extended stress fiber growth model with focal adhesion formation, International Journal of Solids and Structures, 2017.
  [ https://doi.org/10.1016/j.ijsolstr.2017.08.023 ]

• Keshavanarayana, Pradeep (2019) Experimental and numerical investigations of stress fibre reorientation in biological cells. PhD Thesis.  [ http://theses.gla.ac.uk/id/eprint/41149 ]

• PhD, University of Glasgow, UK 2019

• MSc, University of Stuttgart, Germany, 2014

• BTech, National Institute of Technology Karnataka, India. 2012