BIO/BME Faculty Search Seminar; Dr. Kaustav Bera

Title: "Shining Light on Complex Tissues: Engineering strategies for modeling development and disease across time and scale."

Abstract: During development, aging, and disease progression, tissues undergo continuous changes in their mechanical properties. Landmark studies have shown that both the solid and fluid surroundings play central roles in regulating cell behavior. Although in vitro tissue models have enabled fundamental and translational insights into pathophysiology, most fail to capture the temporally evolving dynamics of in vivo tissues. Accurately modeling physiological processes therefore requires accounting for relevant tissue components across length scales and incorporating their dynamic evolution over time. This talk will focus on recently developed tools to control and study the effects of the fluid and solid aspects of the tissue microenvironment. The first part will describe how microfluidic platforms can uncover previously underappreciated physical cues, such as the viscosity of extracellular fluids, that influence cell behavior and cancer progression. I will then show how biophysical modeling can be used to identify new sensory mechanisms by which cells probe their surroundings, and how predictions from these models can be experimentally validated using advanced microscopy, bioengineering tools, and animal models. The second part will focus on engineering the solid microenvironment of tissues using phototunable biomaterials whose mechanical properties can be altered with spatiotemporal precision. By combining these materials with miniature three-dimensional tissues known as organoids, multicellular tissue behavior can be controlled and studied in vitro. I will demonstrate how changes in tissue shape generate mechanical forces that are sensed by cell nuclei and influence cell fate decisions. Finally, I will show how phototunable hydrogels provide a powerful in vitro platform to model and study intestinal crypt fission, a key process underlying intestinal development and regeneration. Overall, this work demonstrates how engineered in vitro models can unravel novel insights into cell behavior during healthy functioning and diseased states. It also establishes the foundation for building platforms with physiologically relevant components and spatiotemporal tunability that can uncover fundamental biological mechanisms and enable translational studies, informing not only the design of effective treatments but also the optimal timing of intervention.