Research Interests

The physics of virus life cycle

We focus on the mechanical and physical principles governing key stages of the viral life cycle: entry, replication, and egress. During entry, we study how viruses exploit cellular mechanics and membrane deformation to penetrate host cells. In the replication phase, we investigate how viruses restructure the cellular internal architecture and drive the formation of membrane-bound and membrane-less viral replication factories. For egress, we analyze the mechanical processes that allow viruses to overcome intracellular barriers and exit the host cell. By integrating these stages, we aim to uncover physical mechanisms that could inform the development of novel antiviral strategies.

Complex Membrane Structures in the Cell

Cellular membranes can form remarkably complex, high-curvature structures, such as the interconnected networks of the endoplasmic reticulum and Golgi apparatus, caveolar invaginations, and the intricate morphology of mitochondria. The dynamics and organization of these structures are tightly linked to cellular function. The formation of such highly curved membrane compartments is enabled by curvature-inducing proteins and the non-uniform distribution of lipids between the two membrane monolayers. To investigate these systems, we use membrane elasticity theory to understand how mechanical properties—such as the presence of curvature-inducing proteins, lipid composition gradients, interactions with the cytoskeleton, and osmotic pressure differences—govern the structure and stability of these membrane compartments.

Complex Membrane Structures in the Cell06

Complex Membrane Structures in the Cell05

Complex Membrane Structures in the Cell04

Complex Membrane Structures in the Cell03

Complex Membrane Structures in the Cell02

Complex Membrane Structures in the Cell01

Membrane-less Organelles Mechanics

Membraneless organelles are biomolecular condensates formed through liquid-liquid phase separation of proteins and RNA or DNA molecules. These structures have emerged as key players in the spatial and functional organization of the cell interior and are integral to numerous biological processes, including RNA metabolism (transcription, splicing, and decay), DNA repair and replication, protein quality control and degradation, and signal transduction. By localizing specific biomolecules, these organelles enable the spatial and temporal regulation of cellular functions, enhance reaction rates, buffer cellular stress, and maintain homeostasis. Interestingly, several viruses exploit these mechanisms, forming membrane-less organelles that serve as viral replication factories, concentrating viral components for efficient assembly. The size and shape of these compartments are critical to their function. Our research focuses on understanding the mechanical properties of these organelles and developing theoretical and computational frameworks to predict their size distributions and shape deformations, particularly as virions form within them.

Fusion (viral entry) and fission (viral release) are critical steps in the enveloped virus life cycle. As a result, both viruses and host cells have evolved opposing mechanisms to control the magnitude of these energy barriers to suit their needs. Viruses have developed strategies to lower the energy barriers, facilitating their entry into cells via the plasma and endosomal membranes. In contrast, cells have evolved mechanisms to increase these energy barriers, strengthening their defenses against viral invasion. Our interest is to use physical modeling and computer simulations to better understand this tug-of-war between host and pathogen.

Theory of Membrane Fusion and Fission

Membrane topological changes are essential for numerous biological processes and are fundamental to life. Membrane fusion occurs during fertilization, muscle cell formation, and intercellular and extracellular trafficking. Membrane fission plays a key role in processes such as exocytosis, mitochondrial division, cytokinesis, reshaping of the endoplasmic reticulum and Golgi apparatus, and the release. Despite the diversity of these processes, they share a common pathway involving a series of lipid rearrangement steps. The energy associated with these steps determines the energy barriers to membrane fusion and fission, and the rates at which these processes occur.