- Abhishek Chaudhuri
Dynamics of bio-polymers : Generation, transmission and response to mechanical stress
Cytoskeleton is a complex and dynamic structure consisting of different kinds of semiflexible filaments and motor proteins rendered active by the hydrolysis of chemical fuel like ATP and GTP. In this talk, I will discuss both individual and collective dynamics of such filaments in the presence of activity. First we shall formulate and characterize a model to describe the dynamics of a semiflexible polymer in the presence of activity due to motor proteins attached irreversibly to a substrate, and a transverse pulling force acting on one end of the filament. Next I will discuss how active mechanical stresses generated on the surface due to contractility and remodelling of active filaments can drive molecular clustering and segregation of cell surface molecules. I will discuss its consequences on the spatiotemporal regulation of chemical reactions on the cell surface.
 A. Chaudhuri and D. Chaudhuri Soft Matter 12, 2157 (2016)
 A. Chaudhuri, B. Bhattacharya, K. Gowrishankar, S. Mayor, M. Rao PNAS 108, 14825 (2011)
- Anirban Sain
How proteins form patterns on membrane vesicles and deform them
Shape of membrane vesicles can change drastically when bio-active proteins bind onto the vesicle surface. The proteins do so by controlling the local curvature of the membrane. We will discuss two such examples, a) clathrin mediated endocytosis in eukaryotic cells, and b) FtsZ driven tubulation of membrane vesicles. In both cases the proteins form interesting patterns on the membrane surface. The resulting vesicle deformation turns out to an interplay of the topology of the closed surface, membrane elasticity and intrinsic curvature of the proteins , which are often powered by active forces.
- Arnab Saha
Determining Physical Properties of the Cell Cortex
Actin and myosin assemble into a thin layer of a dynamic network underneath the membrane of eukaryotic cells. This network generates the forces that drive cell- and tissue-scale morphogenetic processes. The effective material properties of this active network determine large-scale deformations and other morphogenetic events. For example, the characteristic time of stress relaxation (the Maxwell time) in the actomyosin sets the timescale of large-scale deformation of the cortex. Similarly, the characteristic length of stress propagation (the hydrodynamic length) sets the length scale of slow deformations, and a large hydrodynamic length is a pre-requisite for long-ranged cortical flows. Here we introduce a method to determine physical parameters of the actomyosin cortical layer in vivo directly from laser ablation experiments. For this we investigate the cortical response to laser ablation in the one-cell-stage Caenorhabditis elegans embryo and in the gastrulating zebrafish embryo. Our method provides an accurate and robust means for measuring physical parameters of the actomyosin cortical layer. It can be useful for investigations of actomyosin mechanics at the cellular-scale and can provide insights into the active mechanics processes that govern tissue-scale morphogenesis.
- Arpan Bannerjee
A complex systems approach to multisensory perception
The Cognitive Brain Lab is engaged in understanding the systems-level neurobiology underlying perception and action. I will present an example from multisensory speech perception where perceptual categorization can be controlled by one psychophysical parameter, the temporal asynchrony between auditory and visual stimuli. I will further elucidate the neural mechanisms underlying the integration of multisensory information using fMRI and EEG experiments. Finally, I will show how dynamic systems model can capture the behavioral response and neural dynamics observed in the macroscopic EEG data.
- Bidisha Sinha
Understanding the role and regulation of plasma membrane fluctuations by interference microscopy
Shape fluctuations of the plasma membrane are ubiquitous. Besides reflecting the mechanical state of the membrane, in nucleated cells they are proposed to affect spatial organization of molecules on it. The origin, regulation and role of membrane fluctuations is therefore integral to the basic understanding of membrane function. We provide an in-depth study of spatio-temporal fluctuations of the basal plasma membrane in adherent nucleated cells using interference imaging. Similar amplitude of spatial undulations (~ 4-8 nm) were observed for interphase cells in three cell lines (HeLa, CHO, C2C12) while being significantly suppressed in mitotic (HeLa) cells. ATP dependent processes increase temporal fluctuations but resulted in the flattening of spatial undulations. Though activities involving actin polymerization and myosin-II separately can enhance temporal fluctuations, the intact cortex suppresses both spatial and temporal fluctuations. We also find that membrane fluctuations are not necessarily uniform across the cell surface. In HeLa cells transient localized peaks in temporal fluctuations lead to short length scales (~ 2.16 µm x 2.16 µm) heterogeneity that is enhanced by ATP driven activities and suppressed by the cytoskeleton. We observe fluctuations to be regulated when in response to de-adhesion from the substrate, the amplitude of fluctuations is kept constant despite the cellular volume reduction, enhanced endocytosis and cortex thickening. A loss of this regulation by cholesterol depletion results in reduction of amplitude and a concomitant increase of propensity of membrane rupturing on osmotic stress. Fluctuations correlate with the resting membrane potential in Neuro2A cells and differentiation state in C2C12 myotubes.
- Collins Assisi
- Debasish Chaudhuri
Morphology, localization and segregation of chromosomes in bacteria
Bacterial chromosome typically consists of a mm long circular DNA and associated crosslinking proteins. It self organizes into a nucleoid, which is compacted 1000 folds, and confined inside a micron-sized cell. Strong confinement, cross-linking, and molecular crowding of cytosol are expected to play important role in nucleoid morphology and dynamics. A number of recent experiments showed emergence of species independent chromosome morphology, suggesting a more physical origin of it. Micromanipulation of bacterial cell shape proved its connection to nucleoid shape. We use a polymer based model of chromosome in the presence of confinement and depletants to show how the robust shape, positioning and segregation of chromosomes after replication can be explained physically.
- Gabriel Mindlin
- Why neuroscience needs biomechanics: the example of birdsong production
- The dynamical origin of complex motor pattern discussion session title: What happens when dynamics meets biology
- Gautam Menon
Spatio-temporal dynamics of nuclear fluctuations
Fluctuations of the cell nucleus provide specific insights into what happens within them i.e. the dynamics of chromatin contained inside. I will discuss a model for such fluctuations, the predictions it makes and suggestions for experiments that probe compaction states of chromatin as a consequence of its interaction with the proteins that compact it. These results provide some insights into how one might think about Waddington's epigenetic landscape for the stem cell state.
- Guillaume Salbreux
Physics of epithelial folding
Three-dimensional deformations of epithelia play a fundamental role in tissue morphogenesis. The shape of an epithelium is determined by mechanical stresses acting within the tissue cells and from the outside environment. Here we introduce a three-dimensional vertex model which allows to represent the shape of a tissue in three dimensions by a set of vertices. In the model, the motion of vertices is set by apical, lateral and basal surface and line tensions, as well as intracellular pressures and external forces. Using this framework, we discuss how patterned force generation in an epithelium can drive biological tissue folding in cyst formation, fold formation in the Drosophila wing disc, and in pancreatic tumour formation.
- Hilda Cerdeira
The influence of hubs in the structure of a neuronal network during an epileptic seizure
In this work, we propose changes in the structure of a neuronal network with the intention to provoke strong synchronization to simulate episodes of epileptic seizure. Starting with a network of Izhikevich neurons we slowly increase the number of connections in selected nodes in a controlled way, to produce (or not) hubs. We study how these structures alter the synchronization on the spike firings interval, on individual neurons as well as on mean values, as a function of the concentration of connections for random and non-random (hubs) distribution. We also analyze how the post-ictal signal varies for the different distributions. We conclude that a network with hubs is more appropriate to represent an epileptic state.
- Maithreyi Narasimha
Exploring the origins of heterogeneity and collectivity in cell behaviour during morphogenesis: lessons from a Drosophila epithelium
Tissue sculpting during development and upon wounding relies on dynamic and heterogeneous cell behaviors that need to be coordinated in space and time. The origin of these heterogeneities (which include both stochastic and collective cell behaviours) and the mechanisms that underlie their coordination remain poorly understood. One model in which we have investigated both is the amnioserosa, an active participant during Drosophila dorsal closure, a model for wound healing. Using targeted (single cell) genetic and nanoscale laser perturbations, 4D confocal microscopy and quantitative morphodynamics, we investigate the molecular and physical bases of individual cell behaviours (pulsed apical constriction and cell delamination/extrusion) and their coordination. We find that differences in cell behavior result from emergent differences in the spatial organization and dynamics of the actomyosin and microtubule cytoskeleton. We further find that changes in actomyosin organization and dynamics depend on the integrity and dynamics of the microtubule cytoskeleton. In my presentation, I will provide evidence that suggests mechanisms that underlie this dependence and its consequences for membrane protein distribution and force generation. I will also describe experiments that demonstrate that stochastic fluctuations in cell signaling and anisotropies in cytoskeletal tension contribute to the emergent polarisation of the cytoskeleton. Our work uncovers an intricate interplay between the actomyosin and microtubule cytoskeleton and between mechanical and chemical cues in multicellular sensing and the local control of cell behavior.
- Mandar Inamdar
Quantifying and modeling deformation patterns during collective cell migration in MDCK epithelia.
Cells in spreading epithelial colonies on substrates are subject to mainly three types of active mechanical forcing: 1) motile forces, 2) dipolar stresses due to actomyosin contractility and 3) stresses due to cell division and death. In a number of cases, at the boundary, tissue is also additionally subjected to contractile forces from actomyosin cable and pulling forces from the so called leader-cells. Interplay of these driving forces influences the rheology of spreading epithelial cell colonies and also sculpts their shape with a combination of cellular shape modifications and T1 transitions. Using the newly developed triangulation method implemented in TissueMiner, We have quantified the relative contributions of cell shape changes and T1 transitions in small colonies of MDCK epithelia and supplemented these findings with Vertex Model simulations in parallel. We observe that, though the activity in the interior of colonies can modify cell elongation and T1 transition dynamics, the overall colony shape is greatly correlated with the location and migration of leader cells, as well as the contractility of actomyosin cable at the boundary.
- Mogens Jensen
Mode Hopping and Arnold Tongues in Cell Dynamics
Oscillating genetic patterns have been observed in networks related to the transcription factors NFkB, p53 and Hes1. We have identified the central feed-back loops leading to oscillations. By applying an external periodic signal, it is possible to lock the internal oscillation to the external signal. For the NF-kB systems in single cells we have observed that the two signals lock when the ration between the two frequencies is close to basic rational numbers . The resulting response of the cell can be mapped out as Arnold tongues. When the tongues start to overlap we may observe a chaotic dynamics of the concentration in NF-kB . The group of Savas Tay (ETH, Zurich) has in single cell dynamics of the NF-kB system observed transitions rom one tongue to the other when they overlap. We investigate this effect by Gillespie simulations and observe mode hopping transitions between different tongues in good agreement with the experiments . The distribution of waiting times between subsequent mode hoppings follow a stretched exponential indicating strong correlations. The mode hopping dynamics in the stochastic system resembles very much the chaotic dynamics of the deterministic system .
 M.H. Jensen and S. Krishna, ""Inducing phase-locking and chaos in cellular oscillators by modulating the driving stimuli"", FEBS Letters 586, 1664-1668 (2012).
 M.L. Heltberg, R. Kellogg, S. Krishna, S. Tay and M.H. Jensen, ""Noise-induced NF-kB Mode Hopping Enables Temporal Gene Multiplexing"" Cell Systems 3, p532–539.e3, 21 December (2016).
- Namrata Gundiah
Mechanobiology of cell-matrix adhesions under cyclic stretch
- Pramod Pullarkat
Actin in axons: contributions to dynamics and mechanics
The talk will cover two ongoing experiments that reveal unexpected roles played by f-actin in axons. The first part will discuss dynamics of f-actin in artificially pulled membrane nano-tubes. These tubes exhibit actin based contractility that is independent of myosin-II. We will discuss possible mechanism(s) for the origin of this contractility. The contractile response is akin to that exhibited by filopodia in certain cell types. The second part of the talk will cover mechanical response of axons to stretch deformations. Unlike in cells like fibroblasts (or cross-linked in-vitro biopolymer gels) where one see a strain stiffening response, axons exhibit a strain softening behaviour. The experiments also show that f-actin is the main resistive component to mechanical stretch in axons.
- Raghunath Chelakkot
On the Growth and Form of Shoots
Growing plant stems and shoots exhibit a variety of shapes that embody growth in response to various stimuli. Building on experimental observations, we provide a quantitative biophysical theory for these shapes by accounting for the inherent observed passive and active effects: (i) the active controllable growth response of the shoot in response to its orientation relative to gravity, (ii) proprioception, the shoot's growth response to its own observable current shape, and (iii) the passive elastic deflection of the shoot due to its own weight, which determines the current shape of the shoot. Our theory separates the sensed and actuated variables in a growing shoot and results in a morphospace diagram in terms of two dimensionless parameters representing a scaled local active gravitropic sensitivity, and a scaled passive elastic sag. Our computational results allow us to explain the variety of observed transient and steady morphologies with effective positive, negative and even oscillatory gravitropic behaviours, without the need for ad hoc complex spatio-temporal control strategies in terms of these parameters. More broadly, our theory is applicable to the growth of soft, floppy organs where sensing and actuation are dynamically coupled through growth processes via shape.
- Ramanujan Srinivasan
Understanding the basis of diversity in cytoskeleton organisation in prokarya
While the eukaryotic cytoskeleton is highly conserved, the bacterial homologs exhibit a wide range of diversity. We have previously established fission yeast, Schizosaccharomyces pombe as a cellular model to understand form and dynamic nature of the prokaryotic cytoskeleton. We had earlier shown that the cell division protein FtsZ self-organizes into ring-like structures. These ring-like structures seemed to be formed by a process of spooling of pre-formed linear filaments. New insights gained into the mechanism of organization of FtsZ rings and arrangement of filaments will be discussed. Further, we discovered novel dynamic behaviours and unique filament architectures in a subset of actin-like proteins. These recent findings will be further discussed and in particular I’ll talk about an actin that assembles into tubular structure. Our studies provide new insights into the mechanisms by which diverse bacterial cytoskeletal proteins organize and function.
- Richa Rickhy
Formation and function of cellular architecture in Drosophila blastoderm embryos
Metazoan embryos provide a model system to study how epithelial like polygonal cellular architecture develops and interacts with morphogen gradients. We have used the syncytial blastoderm embryo to study the onset of polygonal epithelial like architecture in otherwise incomplete cells and interaction with the spread of morphogen gradients. We find that the plasma membrane is organized as a hexagon dominated polygonal array from cycle 12 onwards. This polygonal organization depends upon the length of the lateral plasma membrane domain and the polarized distribution of junctional proteins. Depletion of proteins such as Bazooka results in change from hexagon to pentagon dominated plasma membrane organization. Depletion of junctional protein DE-Cadherin results in loss of polygonal organization showing that it is necessary for initiation of the polygonal network. Morphogen gradients Bicoid and Dorsal pattern the body axis in the embryo and have distinct spreading kinetics in the syncytial embryo. The organized syncytial architecture is likely to play a role in restricting cytoplasmic proteins also. We find that phospholipid interacting protein linked to the syncytial plasma membrane and localized to the anterior like Bicoid results in its spread in the antero-posterior axis in a manner similar to Bicoid. Our studies of characterization of the syncytial architecture initiate its use as a simple model system to study development of cellular properties of epithelial like organization and its impact on patterning events in early embryogenesis.
- Shashi Thutupalli
- Sridharan Devrajan
Theoretical and computational approaches to cognitive neuroscience
Our brain is arguably the most complex biological organ. The large number of brain cells or neurons (~100 billion) and their connections (several trillions) produce an amazing diversity of neural dynamics. Understanding essential principles by which this complex machinery produces cognitive function is a fundamental challenge for 21st century science. Theoretical and computational approaches, including Bayesian modeling, data mining and machine learning, provide a powerful paradigm for meeting this challenge. I will present several ongoing efforts in our lab that seek to understand the neural basis of cognition by combining experimental and computational approaches. First, I will show how machine learning, applied to a cohort of several thousand functional MRI scans, has provided key insights into information flow patterns in the brain during distinct cognitive states. Then, I will describe how computational neural network models are helping us understand the limits of the capacity of human attention. I will conclude by discussing key challenges and opportunities at the interface of theory, computational science and neuroscience.
- Srinavasa Chakravarthy V
The basal ganglia as an exploration engine
- Suhita Nadkarni
Sophisticated Synapses - a quantitative insight into crucial components of higher function
Synaptic transmission is essential to all information processing in the nervous system. Changes in the strength of synaptic transmission, termed synaptic plasticity, is the cellular underpinning of learning and memory. Synapses are specialized components of neuronal networks comprising a plethora of molecular signaling cascades that operate over multiple timescales to give rise to intricate spatiotemporal patterns of activity. Minute components of this complex system can have far reaching consequences that transcend levels of organization, from molecules to behavior. Most neurological diseases have a synaptic basis. Our ultimate goal is to understand the contribution of each of these pathways to higher level function. Our approach is to devise realistic biophysical computational models of these sophisticated neural components that allow for ‘In-Silico’ experiments and make testable predictions. Given the locus of activity in the synapses is constrained to small spatial domains and small number of molecules orchestrate the signaling cascades, it is difficult to make direct measurements. A detailed modeling paradigm can serve as a bridge between experiments and theory. I will discuss critical role of different sources of calcium in short-term plasticity and its implication to Alzheimer’s Disease.
- Sumantra Chatterji
To be or not to be afraid: computing what is safe or dangerous
Although we think of memories as rooted in the past, they have a profound influence on how we respond to events in the future. In this sense, what we learn from past experiences – our memories – not only give shape to our sense of who we are, but also how we interact with the world around us. Memories come in many different flavors – some experiences are memorable, others forgettable. Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the rapid and efficient encoding of emotional memories can become maladaptive – severe stress often turns them into a source of prolonged anxiety.
Fear memories are crucial for survival. However, excessive generalization of such memories, characterized by a failure to discriminate dangerous from safe stimuli, is common in anxiety disorders. Neuronal encoding of the transition from cue-specific to generalized fear is poorly understood. We identified distinct neuronal populations in the lateral amygdala (LA) of rats that signaled generalized versus cue-specific associations and determined how their distributions switched during fear generalization. Notably, the same LA neurons that were cue-specific before the behavioral shift to generalized fear lost their specificity afterwards, thereby tilting the balance of activity toward a greater proportion of generalizing neurons. These results provide, for the first time, a cellular basis in the amygdala for the alteration of emotional states from normal to pathological fear.
- Supratim Ray
Understanding the role of brain oscillations in cortical processing
Brain signals often show oscillations at different frequencies, which are tightly coupled to different behavioral states. We are interested in a high-frequency oscillation called “gamma” (30-80 Hz), which is modulated by high-level cognitive processes such as attention, memory, and meditation. I will discuss some characteristics of gamma oscillations, in particular how varying the color, size and contrast of the stimulus can modulate gamma oscillations, and how these oscillations can be disrupted by introducing discontinuities in the stimulus.
- Tamal Das
Mechanobiology of Collective Cell Migration
Collective cell migration refers to the process of many cells migrating as a cohesive group, with each individual cell correlating its movement with that of its neighbors. During collective migration, how physical forces exactly contribute to cell-cell interactions and biochemical signaling remains poorly understood. To this end, we are investigating how inter-and intra-cellular forces control different biochemical signaling pathways to support the collective cell migration of epithelial cells. Relevantly, we have discovered a comprehensive molecular mechanism explaining why cell velocities predominantly follow the cell-cell pulling forces. In addition, very recently, we have provided the direct experimental evidence of a cellular level shared-decision making process, in which the selection of leader cells at the interface depends on the dynamics and the biophysical state of the follower cells within a collective. Taken together, our research endeavors are revealing various new mechanobiological and therapeutically targetable aspects of wound healing and cancer.
- Upinder Bhalla
Cascades and selectivity in networks of sequence-detecting neurons
- Vijay Krishnamurthy