ResearchPad - physics-of-living-systems https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Dynamics of pattern formation and emergence of swarming in <i>Caenorhabditis elegans</i>]]> https://www.researchpad.co/article/elastic_article_11937 Many animals collectively form complex patterns to tackle environmental difficulties. Several biological and physical factors, such as animal motility, population densities, and chemical cues, play significant roles in this process. However, very little is known about how sensory information interplays with these factors and controls the dynamics of pattern formation. Here, we study the direct relation between oxygen sensing, pattern formation, and emergence of swarming in active Caenorhabditis elegans aggregates. We find that when thousands of animals gather on food, bacteria-mediated decrease in oxygen level slows down the animals and triggers motility-induced phase separation. Three coupled factors—bacterial accumulation, aerotaxis, and population density—act together and control the entire dynamics. Furthermore, we find that biofilm-forming bacterial lawns including Bacillus subtilis and Pseudomonas aeruginosa strongly alter the collective dynamics due to the limited diffusibility of bacteria. Additionally, our theoretical model captures behavioral differences resulting from genetic variations and oxygen sensitivity.

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<![CDATA[Polar pattern formation induced by contact following locomotion in a multicellular system]]> https://www.researchpad.co/article/elastic_article_6348 The cells of animals and many other living things are able to migrate together in groups. This collective cell migration plays crucial roles in many processes in animals such as forming organs and limbs, and healing wounds.

A soil-dwelling amoeba called Dictyostelium discoideum – or just Dicty for short – is commonly used as a model to study how groups of cells migrate collectively. Individual Dicty cells may live alone but sometimes many cells come together to form a larger mobile structure called a “slug”. Chemical signals coordinate how the cells collectively migrate to form the multicellular slug. Mutant Dicty cells that lack these chemical signal processes can still move together as a band that travels across a surface. This movement resembles a type of collective motion that has previously been observed in physics experiments using self-propelled particles. However, it remains unclear how this collective behavior works.

Hayakawa et al. have now combined genetics, cell biology and computational approaches to study how groups of the mutant Dicty cells migrate together. The experiments showed that the traveling band is dynamically maintained by cells joining or leaving, and that this turnover is caused by simple interactions between the cells known as “contact following locomotion”.

Contact following locomotion has been also reported in mammalian cells so the findings of Hayakawa et al. may aid research into how animals develop and how errors in cell migration may lead to diseases. Further studies are required to find out whether other cells showing contact following locomotion also travel in a band.

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<![CDATA[Shape selection and mis-assembly in viral capsid formation by elastic frustration]]> https://www.researchpad.co/article/N3fa65027-b118-46b2-906e-665ae87fd105

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses. Using elasticity theory and coarse-grained simulations, we analyze the conditions required for these processes to occur and their significance for empty virus self-assembly. We find that the outcome of the assembly can be recast into a universal phase diagram showing that viruses with high mechanical resistance cannot be self-assembled directly as spherical structures. The results of our study justify the need of a maturation step and suggest promising routes to hinder viral infections by inducing mis-assembly.

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<![CDATA[The transpeptidase PBP2 governs initial localization and activity of the major cell-wall synthesis machinery in E. coli]]> https://www.researchpad.co/article/N4dc58d6a-8962-4005-80c8-ecf8d81c99f8

Bacterial shape is physically determined by the peptidoglycan cell wall. The cell-wall-synthesis machinery responsible for rod shape in Escherichia coli is the processive 'Rod complex'. Previously, cytoplasmic MreB filaments were thought to govern formation and localization of Rod complexes based on local cell-envelope curvature. Using single-particle tracking of the transpeptidase and Rod-complex component PBP2, we found that PBP2 binds to a substrate different from MreB. Depletion and localization experiments of other putative Rod-complex components provide evidence that none of those provide the sole rate-limiting substrate for PBP2 binding. Consistently, we found only weak correlations between MreB and envelope curvature in the cylindrical part of cells. Residual correlations do not require curvature-based Rod-complex initiation but can be attributed to persistent rotational motion. We therefore speculate that the local cell-wall architecture provides the cue for Rod-complex initiation, either through direct binding by PBP2 or through an unknown intermediate.

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<![CDATA[Sperm chemotaxis is driven by the slope of the chemoattractant concentration field]]> https://www.researchpad.co/article/N5a9d7c48-7850-4b90-aec4-6131671e0ab9

Spermatozoa of marine invertebrates are attracted to their conspecific female gamete by diffusive molecules, called chemoattractants, released from the egg investments in a process known as chemotaxis. The information from the egg chemoattractant concentration field is decoded into intracellular Ca2+ concentration ([Ca2+]i) changes that regulate the internal motors that shape the flagellum as it beats. By studying sea urchin species-specific differences in sperm chemoattractant-receptor characteristics we show that receptor density constrains the steepness of the chemoattractant concentration gradient detectable by spermatozoa. Through analyzing different chemoattractant gradient forms, we demonstrate for the first time that Strongylocentrotus purpuratus sperm are chemotactic and this response is consistent with frequency entrainment of two coupled physiological oscillators: i) the stimulus function and ii) the [Ca2+]i changes. We demonstrate that the slope of the chemoattractant gradients provides the coupling force between both oscillators, arising as a fundamental requirement for sperm chemotaxis.

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<![CDATA[Stochastic yield catastrophes and robustness in self-assembly]]> https://www.researchpad.co/article/Nc5398b15-af2d-49a6-90a9-80eee7556bc0

A guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.

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<![CDATA[Overtone focusing in biphonic tuvan throat singing]]> https://www.researchpad.co/article/Nea092d48-f105-4ebd-91bd-36979d37b401

Khoomei is a unique singing style originating from the republic of Tuva in central Asia. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic magnetic resonance imaging, and vocal tract modeling to demonstrate how biphonation is achieved by modulating vocal tract morphology. Tuvan singers show remarkable control in shaping their vocal tract to narrowly focus the harmonics (or overtones) emanating from their vocal cords. The biphonic sound is a combination of the fundamental pitch and a focused filter state, which is at the higher pitch (1–2 kHz) and formed by merging two formants, thereby greatly enhancing sound-production in a very narrow frequency range. Most importantly, we demonstrate that this biphonation is a phenomenon arising from linear filtering rather than from a nonlinear source.

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<![CDATA[Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior]]> https://www.researchpad.co/article/Nd8849615-3b15-4df6-81b4-e5f774561a49

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein’s globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism.

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<![CDATA[Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones]]> https://www.researchpad.co/article/Na4a94f1d-a35d-46c7-95d9-26faa13ff4fa

Hsp70 molecular chaperones are abundant ATP-dependent nanomachines that actively reshape non-native, misfolded proteins and assist a wide variety of essential cellular processes. Here, we combine complementary theoretical approaches to elucidate the structural and thermodynamic details of the chaperone-induced expansion of a substrate protein, with a particular emphasis on the critical role played by ATP hydrolysis. We first determine the conformational free-energy cost of the substrate expansion due to the binding of multiple chaperones using coarse-grained molecular simulations. We then exploit this result to implement a non-equilibrium rate model which estimates the degree of expansion as a function of the free energy provided by ATP hydrolysis. Our results are in quantitative agreement with recent single-molecule FRET experiments and highlight the stark non-equilibrium nature of the process, showing that Hsp70s are optimized to effectively convert chemical energy into mechanical work close to physiological conditions.

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<![CDATA[Bridging the gap between single-cell migration and collective dynamics]]> https://www.researchpad.co/article/Nc850d74f-eff4-4ae3-a19f-b870d669a115

Motivated by the wealth of experimental data recently available, we present a cellular-automaton-based modeling framework focussing on high-level cell functions and their concerted effect on cellular migration patterns. Specifically, we formulate a coarse-grained description of cell polarity through self-regulated actin organization and its response to mechanical cues. Furthermore, we address the impact of cell adhesion on collective migration in cell cohorts. The model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet allows for the efficient simulation of confluent tissues. In confined circular geometries, we find that specific properties of individual cells (polarizability; contractility) influence the emerging collective motion of small cell cohorts. Finally, we study the properties of expanding cellular monolayers (front morphology; stress and velocity distributions) at the level of extended tissues.

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<![CDATA[Origin and role of the cerebrospinal fluid bidirectional flow in the central canal]]> https://www.researchpad.co/article/N20d99b54-c7ff-404b-8d2d-895f10fee16a

Circulation of the cerebrospinal fluid (CSF) contributes to body axis formation and brain development. Here, we investigated the unexplained origins of the CSF flow bidirectionality in the central canal of the spinal cord of 30 hpf zebrafish embryos and its impact on development. Experiments combined with modeling and simulations demonstrate that the CSF flow is generated locally by caudally-polarized motile cilia along the ventral wall of the central canal. The closed geometry of the canal imposes the average flow rate to be null, explaining the reported bidirectionality. We also demonstrate that at this early stage, motile cilia ensure the proper formation of the central canal. Furthermore, we demonstrate that the bidirectional flow accelerates the transport of particles in the CSF via a coupled convective-diffusive transport process. Our study demonstrates that cilia activity combined with muscle contractions sustain the long-range transport of extracellular lipidic particles, enabling embryonic growth.

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<![CDATA[Nucleolar dynamics and interactions with nucleoplasm in living cells]]> https://www.researchpad.co/article/Na8fa6712-8009-404f-a4b9-1ead4f4b78b2

Liquid-liquid phase separation (LLPS) has been recognized as one of the key cellular organizing principles and was shown to be responsible for formation of membrane-less organelles such as nucleoli. Although nucleoli were found to behave like liquid droplets, many ramifications of LLPS including nucleolar dynamics and interactions with the surrounding liquid remain to be revealed. Here, we study the motion of human nucleoli in vivo, while monitoring the shape of the nucleolus-nucleoplasm interface. We reveal two types of nucleolar pair dynamics: an unexpected correlated motion prior to coalescence and an independent motion otherwise. This surprising kinetics leads to a nucleolar volume distribution, p(V)V-1, unaccounted for by any current theory. Moreover, we find that nucleolus-nucleoplasm interface is maintained by ATP-dependent processes and susceptible to changes in chromatin transcription and packing. Our results extend and enrich the LLPS framework by showing the impact of the surrounding nucleoplasm on nucleoli in living cells.

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<![CDATA[Mechanics and kinetics of dynamic instability]]> https://www.researchpad.co/article/Nb440a75a-f44d-479e-8a6c-707877158406 During dynamic instability, self-assembling microtubules (MTs) stochastically alternate between phases of growth and shrinkage. This process is driven by the presence of two distinct states of MT subunits, GTP- and GDP-bound tubulin dimers, that have different structural properties. Here, we use a combination of analysis and computer simulations to study the mechanical and kinetic regulation of dynamic instability in three-dimensional (3D) self-assembling MTs. Our model quantifies how the 3D structure and kinetics of the distinct states of tubulin dimers determine the mechanical stability of MTs. We further show that dynamic instability is influenced by the presence of quenched disorder in the state of the tubulin subunit as reflected in the fraction of non-hydrolysed tubulin. Our results connect the 3D geometry, kinetics and statistical mechanics of these tubular assemblies within a single framework, and may be applicable to other self-assembled systems where these same processes are at play. ]]>