Monday, September 11 |
07:00 - 08:45 |
Breakfast ↓ Breakfast is served daily between 7 and 9am in the Vistas Dining Room, the top floor of the Sally Borden Building. (Vistas Dining Room) |
08:45 - 09:00 |
Introduction and Welcome by BIRS Staff ↓ A brief introduction to BIRS with important logistical information, technology instruction, and opportunity for participants to ask questions. (TCPL 201) |
09:00 - 09:40 |
Rae Robertson-Anderson: Emergent micro-mechanics of active cytoskeletal composites ↓ The cell cytoskeleton is a composite of protein filaments, including actin, microtubules and intermediate filaments, as well as their associated crosslinking proteins, that is pushed out-of-equilibrium by molecular motors to mediate wide-ranging processes from migration to morphogenesis. The cytoskeleton is, thus, paradigmatic active matter and its composite nature is one of its hallmarks. Yet, state-of-the-art active matter focuses on single force-generating components and substrates. Here, we engineer programmable composites of actin filaments and microtubules that can be versatilely crosslinked and driven by dual motors, kinesin and myosin, to contract, flow, and restructure into diverse morphologies, ranging from interpenetrating scaffolds to phase-separated clusters. We couple optical tweezers microrheology with differential dynamic microscopy and particle-image-velocimetry to demonstrate that composites exhibit emergent rheological properties that arise from cooperativity between actin and microtubules as well as competition between myosin and kinesin. Microtubules confer enhanced force resistance, elastic memory, and ordered dynamics to myosin-driven actin networks, while kinesin and myosin motors compete to delay composite restructuring and suppress de-mixing. Moreover, we find that the nonlinear force response of active composites exhibits emergent high-strength and multi-modal stiffening at intermediate kinesin concentrations and strain rates that vanish at the low and high limits. Our composite designs, along with our robust microscale measurements, offer a powerful platform for active matter interrogation and discovery, and may prove foundational for diverse materials applications from wound-healing to soft-robotics. (TCPL 201) |
09:40 - 10:20 |
Michael Murrell: Energetic constraints on biological assembly and motion ↓ On small length-scales, the mechanics of soft materials may be dominated by their interfacial properties as opposed to their bulk properties. These effects are described by equilibrium models of elasto-capillarity and wetting. In these models, interfacial energies and bulk material properties are held constant. However, in biological materials, including living cells and tissues, these properties are not constant, but are ‘actively’ regulated and driven far from thermodynamic equilibrium. As a result, the constraints on work produced during the various physical behaviors of the cell are unknown. Here, by measurement of elasto-capillary effects during cell adhesion, growth and motion, we demonstrate that interfacial and bulk parameters violate equilibrium constraints and exhibit anomalous effects, which depend upon a distance from equilibrium. However, their anomalous properties are reciprocal, and thus in combination reliably define energetic constraints on the production of work arbitrarily far from equilibrium. These results provide basic principles that govern biological assembly and behavior. (TCPL 201) |
10:20 - 10:40 |
Coffee Break (TCPL Foyer) |
10:40 - 11:20 |
Vivek Shenoy: Chemo-mechanical diffusion waves orchestrate collective dynamics of immune cell podosomes ↓ Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (vertical height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual vertical oscillations and the collective spatiotemporal wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for both the oscillatory growth of individual podosomes and the wave-like dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers within the cluster drives wave-like mesoscale coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments (targeting myosin activity, actin polymerization, and mechanosensitive Rho-ROCK pathway) and the impact of microenvironment stiffness on chemo-mechanical waves. Overall, our integrated theoretical and experimental approach reveals how collective wave dynamics arise from the coupling between chemo-mechanical signaling and actin diffusion, shedding light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy. (TCPL 201) |
11:20 - 12:00 |
John Berezney (TCPL 201) |
11:30 - 13:00 |
Lunch ↓ Lunch is served daily between 11:30am and 1:30pm in the Vistas Dining Room, the top floor of the Sally Borden Building. (Vistas Dining Room) |
14:00 - 14:20 |
Group Photo ↓ Meet in foyer of TCPL to participate in the BIRS group photo. The photograph will be taken outdoors, so dress appropriately for the weather. Please don't be late, or you might not be in the official group photo! (TCPL Foyer) |
17:30 - 19:30 |
Dinner ↓ A buffet dinner is served daily between 5:30pm and 7:30pm in Vistas Dining Room, top floor of the Sally Borden Building. (Vistas Dining Room) |
19:30 - 20:10 |
Moumita Das: From Rigidity to Resilience: How Rigidity Transitions Modulate Bipolymer Network Mechanics in Cells and Tissues (TCPL 201) |
20:10 - 20:50 |
Ming Guo: Nonlinear effect in cell-matrix interactions ↓ In this talk, I will introduce our recent works in quantitatively studying how cells interact with their surrounding extracellular matrix. In particular, I will discuss the critical impact of the matrix nonlinear elasticity in regulating cell-ECM mechanical interactions. For example, the nonlinear stiffening nature of the ECM enables a significantly extended stress dissipation, and the creation of a stiff shell surrounding the cell. These effects have important role in regulating cell-cell communications, as well as mechanobiology of cell-ECM interactions. In addition, I will also show results revealing the critical role of interfacial curvature on cell migratory behaviors. (TCPL 201) |