The self-organization of active particles is governed by their dynamic effective interactions. Such interactions are controlled by the medium in which such active agents reside. Here we study the interactions between active agents in a dense non-active medium. Our system consists of actuated, spinning, active particles embedded in a dense monolayer of passive, or non-active, particles. We demonstrate that the presence of the passive monolayer alters markedly the properties of the system and results in a reversal of the forces between active spinning particles from repulsive to attractive. The origin of such reversal is due to the coupling between the active stresses and elasticity of the system. This discovery provides a mechanism for the interaction between active agents in complex and structured media, opening up opportunities to tune the interaction range and directionality via the mechanical properties of the medium.
Particle-particle interactions determine the state of a system. Control over the range of such interactions as well as their magnitude has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Very recently, effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our systems are 2D colloidal monolayers composed primarily of passive (inactive) colloids, and a very small fraction of active (spinning) ferromagnetic colloids. We find an emergent ultra-long-range attractive interaction induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation timescale below which no attraction is observed. Overall, these results clearly show that, in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials.active matter | nonequilibrium | colloids | monolayer | elasticity A ctive-matter systems have received much interest due to their emergent nonequilibrium phase and collective dynamical behavior. This interest is well founded as some of the most ubiquitous and important biological systems or processes can exhibit such emergent nonequilibrium behavior, which is perhaps most recognizable in macroscopic examples ranging from schools of aquatic organisms like rays or fish (1-3), herds of livestock (4), flocks of birds (5-7), and even a mosh pit at a heavy metal concert (8). Active-matter systems are additionally unique in that such phenomena spans multiple length scales from meter to nanometer. At these smaller length scales, it is clear that such dynamical adaptation and phase separation are necessary to perform many vital biological processes. Dense crowds of cells move collectively through tissue during development and in many of the immune response processes, i.e., wound healing (9). Sea urchin sperm cells have been found to phase separate and organize into arrays of vortices when the density of spermatozoa is large enough (10). In fact, a myriad of biological systems, and experimental systems with biological components, have reported swarming (11-13), flocking (6, 14, 15), spiraling (13, 16), and many more nonequilibrium steady states (17,18). It is clear that, in all these systems, a combination of the activity, shape of the active agents, and the environment lead to effective out-ofequilibrium interactions that determine their steady states. These active-matter systems have ...
Friction, the resistive force between two surfaces sliding past each other, is at the core of a wide diversity of locomotion schemes. While such schemes are well described for homogeneous environments, locomotion based on friction in inhomogeneous environments has not received much attention. Here we introduce and demonstrate the concept of tribotaxis, a motion that is guided by gradients in the friction coefficient. Our system is composed of microwalkers that undergo an effective frictional interaction with biological receptors on the substrate, which is regulated by the density of such receptors. When actuated stochastically, microwalkers migrate to regions of higher friction, much like a chemotactic cell migrates to regions of higher chemoattractant concentration. Simulations and theory based on biased random walks are in excellent agreement with experiments. We foresee important implications for tribotaxis in artificial and natural locomotion in biological environments. DOI: 10.1103/PhysRevLett.113.178101 PACS numbers: 87.85.gj, 81.40.Pq, 87.16.Uv Tribotaxis is the process by which an active object, biotic or abiotic, detects differences in the effective local friction coefficient and moves to regions of higher or lower friction according to a given protocol. The local friction coefficient between an object and a surface is dictated by the effective interactions between both. If these interactions are directional in nature, the friction coefficient is anisotropic. A prominent example of this, being the skin of many animals which feels rough when stroked in one direction, yet soft in the other. The origin of this asymmetry is due to the directionality and ordering of hair or scales sticking out from the surface at a slanted angle, which helps in modulating the effective friction between the skin (or scales) of an animal and the surrounding fluid [1,2]. These types of materials are important in many other processes, such as regulating the flow of complex fluids [3], controlling the motion of cells [4], or even skiing up a mountain.While the motifs that give rise to these asymmetric friction coefficients are rather large, one can envision an alternative microscopic scenario. For example, one can think of exchanging the mechanical texture with a chemical texture in which friction is dominated by the strength and spatial density of reversible bonds between an object and a substrate [5,6]. Moreover, gradients in the spatial density of such ligands produce anisotropic friction coefficients. Live cells, for example, naturally detect surface ligand gradients and move accordingly [7]; this is one of the most important clues for locomotion since cells are constantly encountering surfaces in our bodies. Mimicking this behavior using biological ligand-receptor pairs can potentially allow one to "walk on" and sense different conditions in the vast amounts of interfaces in tissues and organs. In addition, chemically based tribotaxis can be used to locally sense friction in purely synthetic environments. Interestingly, ...
Polyubiquitination by E2 and E3 enzymes is crucial to cell cycle control, epigenetic regulation, and development. The hallmark of the E2 family is the ubiquitin (Ub)-conjugating (UBC) domain that forms a dynamic thioester conjugate with ubiquitin (E2~Ub). Numerous studies have focused on E2 surfaces, such as the Nterminal and crossover helices, that directly interact with an E3 or the conjugated ubiquitin to stabilize the active, "closed" state of the E2~Ub. However, it remains unclear how other E2 surfaces regulate ubiquitin transfer. Here, we demonstrate the helix-turnhelix (HTH) motif of the UBC tunes the intrinsic polyubiquitination activity through distinct functions in different E2s. Interestingly, the E2 HTH motif is repurposed in UBE2S and UBE2R2 to interact with the conjugated or acceptor ubiquitin, respectively, modulating ubiquitin transfer. Furthermore, we propose that Anaphase-Promoting Complex/Cyclosome binding to the UBE2S HTH reduces the conformational space of the flexible E2~Ub, demonstrating an atypical E3-dependent activation mechanism. Altogether, we postulate the E2 HTH motif evolved to provide new functionalities that can be harnessed by E3s and permits additional regulation to facilitate specific E2-E3-mediated polyubiquitination.
The mechanisms that underlie the extensive phenotypic diversity in genetic disorders are poorly understood. Here, we develop a large-scale assay to characterize the functional valence (gain or loss-of-function) of missense variants identified in UBE3A, the gene whose loss-of-function causes the neurodevelopmental disorder Angelman syndrome. We identify numerous gain-of-function variants including a hyperactivating Q588E mutation that strikingly increases UBE3A activity above wild-type UBE3A levels. Mice carrying the Q588E mutation exhibit aberrant early-life motor and communication deficits, and individuals possessing hyperactivating UBE3A variants exhibit affected phenotypes that are distinguishable from Angelman syndrome. Additional structure-function analysis reveals that Q588 forms a regulatory site in UBE3A that is conserved among HECT domain ubiquitin ligases and perturbed in various neurodevelopmental disorders. Together, our study indicates that excessive UBE3A activity increases the risk for neurodevelopmental pathology and suggests that functional variant analysis can help delineate mechanistic subtypes in monogenic disorders.
Active matter systems are able to exhibit emergent non-equilibrium states due to activity-induced effective interactions between the active particles. Here we study the aggregation and dynamical behavior of active rotating particles, spinners, embedded in 2D passive colloidal monolayers, which constitutes one such non-equilibrium process. Using both experiments and simulations we observe aggregation of active particles or spinners whose behavior resembles classical 2D coarsening. The aggregation behavior and spinner attraction depends on the mechanical properties of the passive monolayer and the activity of spinners. Spinner aggregation only occurs when the passive monolayer behaves elastically and when the spinner activity exceeds a minimum activity threshold. Interestingly for the spinner concentrations investigated here, the spinner concentration doesn't seem to change the dynamics of the aggregation behavior. There is also a characteristic cluster size at which the dynamics of spinner aggregation is maximized as drag through the passive monolayer is minimized and the stress applied on the passive medium is maximized. We also show that a ternary mixture of passive particles, co-rotating, and counter-rotating spinners also aggregates into clusters of co and counter-rotating spinners respectively. * These two authors contributed equally † aalexand@mit.edu arXiv:1701.06930v1 [cond-mat.soft]
Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-functionalized substrate. The translational displacement scales with the effective friction induced by a PPI, thus producing a mechanical signal when a binding event occurs. The METRIS assay uses as little as 20 pmols of reagents to measure a wide range of affinities while exhibiting a high resolution and sensitivity. We use METRIS to measure several PPIs that were previously inaccessible using traditional methods, providing new insights into epigenetic recognition.
Protein-lipid interactions constitute a very important class of biological interactions critical for multiple cell and tissue functions. It is believed that most lipid-protein interactions are very weak, with affinities in the 1mM-1μM range. Here we study the interactions of multiple protein lipid binding domains with lipid membranes containing signaling lipids known as phosphatidylinositol phosphates (PIPs) using a new mechanically transduced immunosorbent assay (METRIS). We demonstrate that this assay can measure extremely weak interactions at PIP bilayer concentrations below 1%, which is close to the biological lipid concentration regime. In particular, we have studied the interaction of DrrAWT, DrrAK568A, PH-δ, and 2XFYVE as well as previously unexplored lipid binding domains such as Auxilin 1 (PTEN) and Auxilin 2 (GAK) against a wide palette of PIPs. Our results confirm that each of these domains interacts specifically with a PIP partner. In the case of Auxilin 1 and Auxilin 2, both proteins in the Clathrin endocytotic pathway, we find that their PTEN-like domain interacts specifically yet with ultra low affinity with PI3P and PI4P respectively. We have also found a new unknown medium-high affinity interaction between GAK with PI34P2. Our work, thus, provides a direct and robust method to measure and catalog protein lipid interactions which are important in many processes such as signaling and membrane sculpting. Furthermore, this assay can be extended in a straightforward manner to study other interactions such as ligand-receptor or antibody-antigen.
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