Parag Katira


Summary:
The focus of my research is to understand how forces generated by soft-matter interactions in biology can influence various biological phenomena. My current projects study bio-matter interactions at the cellular and tissue levels using computational as well as experimental techniques, and my aim is to understand how mechanics shapes tissues and tumors.

parag1Tissues are nature’s example of active materials that self-regulate and self-heal under the influence of external stimuli. In this project we focus on developing viscoelastic-particle-paste models for describing tissues, where the particles are cells comprising the tissue. We use these models to study how changes in the mechanical properties of cells influence tissue dynamics and collective cell behavior with applications in the prediction and treatment of cancer.

Using the modeling framework described above, we have shown that changes in cellular mechanical properties, especially the increase in cell compliance as observed for cancer cells, can in provide the impetus required for tumor growth and evasion of apoptosis by cancer cells. Furthermore, our simulations show how changes in inter-cellular adhesion influence tumor growth rates and shape evolution.

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The model described above takes into account the mechanical regulation of cell fate and the differences in mechanosensing that might accompany the mechanical property changes occurring in cancer cells. We are currently conducting experiments to quantify these mechanical changes in cells accompanying malignant transformation, by observing the growth and behavior of normal and malignant cells in 3D collagen gels. These experiments are being conducted in collaboration with Dr. Muhammad Zaman at Boston University and Dr. Vernita Gordon in the Physics Department at UT Austin.

Relevant publications and highlights in scientific media describing this research

Katira P, Zaman MH, Bonnecaze RT (2012) “How changes in cell mechanical properties influence
cancerous behavior”; Physical Review Letters 108, 028103

http://physicsworld.com/cws/article/news/2012/jan/18/cell-softening-could-promote-tumour-growth

http://phys.org/news/2012-01-proximate-cancer.html

http://www.futurity.org/health-medicine/cells-mechanical-changes-nudge-cancer/

Transport Mechanics of Metastatic Cancer Cells

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While the project described above focuses on tumorigenesis, i.e. the formation and growth of tumors, as a function of cellular mechanical properties, another key element to cancer progression is metastasis. Metastasis is the process of dissemination of cancer cells from the host tumor and invasion into neighboring as well as distant tissue to form secondary neoplasms. This process is heavily regulated by the ability of cancer cells to migrate through their extra-cellular environment, either individually or as cohorts.

We are working on developing integrated chemo-mechanical models of cell migration incorporating the intra-cellular force generation
machinery as well as the extra-cellular micro- environment’s response to these cellular forces in order to predict cell mobility and metastatic potential under different pathological conditions.