Understanding the role of Substrate Rheology on breast cancer metastasis
Breast cancer (BC) is the most common cancer in women in India. In every 4 minutes in India, one woman is diagnosed with breast cancer (BC), and in every 13 minutes one woman dies of it. Hence, a detailed and deep understanding of the disease progression is much needed for successful therapeutic intervention. One major stage in cancer progression is metastasis in which tumor cells leave their original site and recolonize into a new tissue. For metastatic BC, prognosis is generally poor. Hence, stopping/controlling metastasis is a proposed therapeutic intervention for which understanding cell migration is critical.
In this regards, the gradient in substrate rigidity is known to be an important cue for directed migration. Adherent cells migrate from soft substrate to rigid substrate. However, as the tissues in our body are generally viscoelastic, rigidity (defined by elastic modulus E or the storage modulus G’) is insufficient to describe the rheological complexity of the living systems. For example, in malignant conditions, both the storage and loss modulus (G”) of the breast change significantly. In our earlier work, we have shown that cells migrate from high to low loss modulus substrate which we named as Viscotaxis.
In this work, we wish to explore the role of rigidity and loss modulous on the migration of breas cancer cells. For this purpose, migration of invasive and non-invasive breast cancer cells will be studied on the gels of different combinations of G’ and G”. An attempt will be made to understand the migration mechanism in response to substrate viscoelasticity and deformation. This proposed work will provide us fundamental understanding about migration in breast cancer and will help in finding new therapeutic targets. Additionally, the insight gained should be applicable for other pathophysiological conditions that involve cellular migration.
No formal training in cell culture in needed.
In this project the candidate is expected to prepare various materials, estimates their rheological properties, and then explore the effect of rheological properties on cell fate and cell migration. This project will supervised jointly by Prof. Jyoti Seth and Prof. Abhijit Majumder. To get a flavor of the work, interested candidate may look at the following papers:
1. "“Viscotaxis”-directed migration of mesenchymal stem cells in response to loss modulus gradient" 2021 Acta Biomaterialia
2. Viscoelastic substrate decouples cellular traction force from other related phenotypes, 2021, BBRC
3. Substrate loss modulus promotes the differentiation of SHSY-5Y neuroblastoma cells 2020 Materialia.