Research

 

The Cell-Mechanics lab in the Department of Applied Mechanics, IIT Madras, focuses on studying the mechanics behind health and disease, at cellular and sub-cellular scales. Borrowing upon principles from physical and mathematical sciences, we explore human biology that is responsible for, and is affected by, forces of interaction between mammalian cells and their surroundings.  

 

Focus areas of Cell-Mechanics lab: Metastatic extravasation and invasion, Extracellular vesicles, Blood-cell assay development, Alveolar transport, and Bio-materials development

Some of the currently running research endeavors are in the field of (but not limited to):

Related areas of interest include: 

  • Extravasation mechanics, for circulating tumor cells. 
  • Extracellular vesicles (EV): Characterization of secreted EVs during of pulmonary injury 

  • Biomaterials development: To expose cells to varying mechanical environments of matrix stiffness, architecture, and ligands.

  • Visco-elasticity: of orthotropic collagenous scaffolds, plasma-membrane, extracellular-matrix, etc.

  • Resistive pulse-sensing of suspended mammalian cells such as blood-cells.

 
Our collaborators include Physicists, Biologists, and Clinicians.  Key skills that our research scholars develop are related to mammalian cell-culture, numerous modes of light-microscopy, soft-lithography, instrumentation and signal processing, bio-material synthesis and mechanical characterization, and optics.

(i) Cardio-oncology:

Extravasation involves an orchestrated dance of mechanics of cellular traction, membrane, and endothelial junctional integrity, each affected by cardiovascular drugs.
 
In order to understand the crosstalk between cardiovascular drugs and cancer-progression, we examine  the drug-mediated mechanics of metastatic stages such as loss of cell-to-cell adhesion, gain of cell-to-substrate adhesion, generation of cell-matrix traction, and extravasation of cancer cell across endothelial mono-layer. Since endothelium is frequently the target of cardio-mediatory drugs such as calcium-channel blockers (used to treat hypertension), we quantify the effect of such interventions on cancer-cell extravasation and endothelial junctional integrity. Towards this, we characterize trans-endothelial electrical resistance (TEER), transwell-assay for permeability, as well as direct mechanical characterization of cells using optical tweezers.  

Characterizing the membrane of endothelial cells, during hypertension-therapy, using optical tweezers (A), and endothelial integrity (B) using trans-endothelial electrical resistance (TEER)

(ii) Designing cellular micro-environment

During metastatic migration, cancer cells are exposed to a multiscalar anistropic microenvironment. We are generating tunable engineered microenvironments that allow control over the characteristic properties of cell-microenvironment. In the micrograph (B, below), we see a highly disordered cell-compatible matrix created through processing of silk-fibroin protein, approximating the ordered architecture of ECM surrounding a solid-tumor (A, below)

 

Design of scaffolds for 3D models of cell-migration and growth, exhibiting micro-architecture that approximates the anisotropy around solid tumors.

  

 

(iii) Physics of cell-migration

We are interested in quantifying the forces that a single or a cluster of cells exterts over a 2-D substrate in order to migrate effectively, and under varied physiological/pathological conditions. The micrograph shows a sample image from live-cell traction measurements we conducted for fibroblasts migrating over tunable 2-D substrates.

 

We examine the traction force generated by cells, in both 2D and 3D, under various exogenous stimulatory cues.

 For more information, please feel free to contact us via. email, send in your tweet (@CellMech_IITM) or send us your query through the contact-us link on the top-right of this page.