THE CELL IN A COMPUTER
Essential aspects of cells are chemistry, physics and mechanics.
Motor proteins convert chemical energy to generate mechanical work; intracellular proteins rearrange and self-assemble into a variety of higher order physical structures; cells bear, exert, and transmit mechanical forces by remodeling the cytoskeleton, the adhesions and the extracellular matrix (ECM).
Cytoskeletal physical remodeling, mechanical forces and mechanochemical cell adhesions are key mediators of many cellular processes, such as division, spreading and migration. The processes are critical in several pathologies, including cancer initiation and progression, fibrosis and cardiovascular diseases.
The Computational Biology LAB develops numerical and computational approaches in order to understand the mechanisms underlying cell responses in physiology and disease. These methods help characterizing how molecular and macromolecular components, including single proteins and assemblies of them, modulate complex cell behaviors.
By developing and using these tools, our lab can explain the cell machinery over multiple length and time scales, to relate molecular mechanisms with cell function.
Our main focuses are on the formation and disassembly of adhesion, actomyosin-based contractility and microtubules dynamics.
Mechanics of Cytoskeleton Proteins
Microtubules and actin filaments are filamentous proteins that provide the cell with mechanical resistance to deformations. Microtubules are also used to separate the genetic material during cell division; actin filaments dynamically rearrange into branched or bundled assemblies at the cell leading edges in order to generate, sense and transmit signals. The molecular and macromolecular mechanisms that underlie microtubules and actin filaments functions are not fully explored. In this project, we will combine molecular and macromolecular simulations approaches in order to gain insights into the dynamics of microtubules and actin filaments.
When in contact with a substrate, cells form adhesions that determine spreading, changes in cell shape and migration. Adhesions in cancer cells can promote or inhibit the invasive phenotype. Despite their importance, formation of cells adhesions is not clearly understood. The Computational Biology LAB develops numerical models for understanding adhesions formation on different substrates and how they impact cell shape and migration.
Integrin Activation and Mechanosensing
We run molecular simulations of transmembrane integrin receptors and study their activation pathway.
RGD-binding in adhesions formation
We develop multiscale computational methods to study the effect of RGD-containing peptides on integrin adhesions.