Saraswathibhatla lab is open for business!!

Finally, using an organotypic model mimicking DCIS, we demonstrate that the basement membrane acts as a mechanical insulator, preventing swirling cells from aligning collagen. Thus, after breaching the BM, swirling of BC cells radially aligns collagen (10/11)

Using traction deformation microscopy and fiber model simulations, we confirmed our hypothesis of shear-induced radial contractile stresses in collagen-rich ECMs (9/11)

Based on this, we hypothesized that shear stresses from the swirling motion of cancer cells at the tumor-matrix interface result in radially contractile stresses due to negative normal stress, and such radial stresses, in turn, align col1 radially to facilitate invasion (8/11)

Interestingly, fibrous networks exhibit the property of negative normal stress, where shear forces generate significant contractile forces perpendicular to the shear direction. This was described by Paul Janmey in 2006 and is similar to shear-normal coupling (7/11)

To our surprise, cells migrated tangentially to the tumor-matrix interface in a swirling-like motion. This raised the question: How does the swirling, or tangential, motion of cancer cells at tumor-stroma interface align collagen radially? (6/11)

Prior to the collective invasion, cells radially aligned collagen at the tumor-matrix interface in a TACS-3-like manner, which enabled their collective invasion (5/11)

Consistent with our reasoning, increasing mechanical plasticity of collagen-rich ECMs facilitated invasion, with increasing stiffness potentiating a transition from single cell to collective invasion (4/11)

We reasoned that mechanical plasticity of collagen-rich ECMs will enable cells to remodel collagen and enable their collective invasion. For this, we characterized the mechanics of human tissues and developed collagen-rich biomaterials that mimicked them (3/11)

The radial alignment of collagen fibers (TACS-3) at the tumor-matrix interface is a pathological signature of breast cancer. This was first described by Prof. Paolo Provenzano in late Keely's lab in 2006. However, it is unclear how cancer cells can radially align collagen fibers (2/11)

Despite the current uncertainty of being a scientist, I am excited to share our manuscript demonstrating an interesting mechanism of how swirling motion of breast cancer cells align collagen fibers radially at the tumor-stroma interface to enable their invasion (1/11) @thechaudhurilab.bsky.social