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SeminarPhysics of LifeRecording

The Equation of State of a Tissue

Vikrant Yadav
Yale University
May 23, 2022

An equation of state is something you hear about in introductory thermodynamics, for example, the Ideal gas equation. The ideal gas equation relates the pressure, volume, and the number of particles of the gas, to its temperature, uniquely defining its state. This description is possible in physics when the system under investigation is in equilibrium or near equilibrium. In biology, a tissue is modeled as a fluid composed of cells. These cells are constantly interacting with each other through mechanical and chemical signaling, driving them far from equilibrium. Can an equation of state exist for such a messy interacting system? In this talk, I show that the presence of strong cell-cell interaction in tissues gives rise to a novel non-equilibrium, size-dependent surface tension, something unheard of for classical fluids. This surface tension, in turn, modifies the packing of cells inside the tissue generating a size-dependent density and pressure. Finally, we show that a combination of these non-equilibrium pressure and densities can yield an equation of state for biological tissues arbitrarily far from equilibrium. In the end, I discuss how this new paradigm of size-dependent biological properties gives rise to novel modes of cellular motion in tissues

SeminarPhysics of LifeRecording

Self-organization of chemically active colloids with non-reciprocal interactions

Ramin Golestanian
Max Planck Institute
Apr 7, 2021

Cells and microorganisms produce and consume all sorts of chemicals, from nutrients to signalling molecules. The same happens at the nanoscale inside cells themselves, where enzymes catalyse the production and consumption of the chemicals needed for life. In this work, we have found a generic mechanism by which such chemically-active particles, be it cells or enzymes or engineered synthetic colloids, can "sense" each other and ultimately self- organize in a multitude of ways. A peculiarity of these chemical-mediated interactions is that they break action-reaction symmetry : for example, one particle may be repelled from a second particle, which is in turn attracted to the first one, so that it ends up "chasing" it. Such chasing interactions allow for the formation of large clusters of particles that "swim" autonomously. Regarding enzymes, we find that they can spontaneously aggregate into clusters with precisely the right composition, so that the product of one enzyme is passed on, without lack or excess, to the next enzyme in the metabolic cascade.

SeminarPhysics of LifeRecording

Magic numbers in protein phase transitions

Ned Wingreen
Princeton
Feb 26, 2021

Biologists have recently come to appreciate that eukaryotic cells are home to a multiplicity of non-membrane bound compartments, many of which form and dissolve as needed for the cell to function. These dynamical “condensates” enable many central cellular functions – from ribosome assembly, to RNA regulation and storage, to signaling and metabolism. While it is clear that these compartments represent a type of separated phase, what controls their formation, how specific biological components are included or excluded, and how these structures influence physiological and biochemical processes remain largely mysterious. I will discuss recent experiments on phase separated condensates both in vitro and in vivo, and will present theoretical results that highlight a novel “magic number” effect relevant to the formation and control of two-component phase separated condensates.

SeminarPhysics of Life

“Biophysics of Structural Plasticity in Postsynaptic Spines”

Padmini Rangamani
University of California, San Diego
Oct 27, 2020

The ability of the brain to encode and store information depends on the plastic nature of the individual synapses. The increase and decrease in synaptic strength, mediated through the structural plasticity of the spine, are important for learning, memory, and cognitive function. Dendritic spines are small structures that contain the synapse. They come in a variety of shapes (stubby, thin, or mushroom-shaped) and a wide range of sizes that protrude from the dendrite. These spines are the regions where the postsynaptic biochemical machinery responds to the neurotransmitters. Spines are dynamic structures, changing in size, shape, and number during development and aging. While spines and synapses have inspired neuromorphic engineering, the biophysical events underlying synaptic and structural plasticity of single spines remain poorly understood. Our current focus is on understanding the biophysical events underlying structural plasticity. I will discuss recent efforts from my group — first, a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation and a series of spatial models to study the role of spine geometry and organelle location within the spine for calcium and cyclic AMP signaling. Second, I will discuss how mechanics of membrane-cytoskeleton interactions can give insight into spine shape region. And I will conclude with some new efforts in using reconstructions from electron microscopy to inform computational domains. I will conclude with how geometry and mechanics plays an important role in our understanding of fundamental biological phenomena and some general ideas on bio-inspired engineering.

SeminarPhysics of LifeRecording

Collective signaling oscillations in embryos

Jane Kondev
Brandeis University
Aug 17, 2020
SeminarPhysics of LifeRecording

Collective signaling oscillations in embryos

Alexander Aulehla
EMBL
Aug 13, 2020
SeminarPhysics of Life

Untitled Seminar

Multiple Speakers
Multiple
Jul 31, 2020

The symposium provides an opportunity for ECRs working in biophysical research to get together and to share their research. Although the symposium is primarily aimed at ECRs, we welcome everyone with an interest in biophysical sciences to join in the lively discussions and questions. This half day symposium will feature short talks and flash-talks from a range of ECRs around the biophysics theme. Afterwards there will be a virtual poster session with open discussions. We warmly invite both domestic and international ECRs to present at/attend this event.

SeminarPhysics of Life

Robotic mapping and generative modelling of cytokine response

Paul François
McGill University – Montréal QC – Canada
Jul 29, 2020

We have developed a robotic platform allowing us to monitor cytokines dynamics (including IL-2, IFN-g, TNF, IL-6) of immune cells in vitro, with unprecedented resolution. To understand the complex emerging dynamics, we use interpretable machine learning techniques to build a generative model of cytokine response. We discover that, surprisingly, immune activity is encoded into one global parameter, encoding ligand antigenic properties and to a less extent ligand quantity. Based on this we build a simple interpretable model which can fully explain the broad variability of cytokines dynamics. We validate our approach using different lines of cells and different ligands. Two processes are identified, connected to timing and intensity of cytokine response, which we successfully modulate using drugs or by changing conditions such as initial T cell numbers. Our work reveals a simple "cytokine code", which can be used to better understand immune response in different contexts including immunotherapy. More generally, it reveals how robotic platforms and machine learning can be leveraged to build and validate systems biology models.

SeminarPhysics of Life

Pancreatic α and β cells are globally phase-locked

Chao Tang
Peking University – Beijing China
Jul 29, 2020

The Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of cells in the islet couple and coordinate to give rise to various Ca2+ oscillation patterns and how these patterns are being tuned by paracrine regulation are still elusive. Here we developed a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and found that islets show heterogeneous but intrinsic oscillation patterns. The α and β cells in an islet oscillate in antiphase and are globally phase locked to display a variety of oscillation modes. A mathematical model of islet oscillation maps out the dependence of the oscillation modes on the paracrine interactions between α and β cells. Our study reveals the origin of the islet oscillation patterns and highlights the role of paracrine regulation in tuning them.

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