ABSTRACT
A long-standing question in cell biology is how endocytic vesicles and tubules detach from the plasma membrane in the absence of constriction by dynamin. In this issue of Cell, Simunovic et al. describe an elegant biophysical model in which friction between lipids and BAR-domain proteins drives the scission of elongating membrane tubules.
Subject(s)
Endocytosis , Friction , Cell Membrane , Dynamins , Transport VesiclesABSTRACT
Membrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis. We call this mechanism friction-driven scission (FDS). In cells, motors pull tubes, particularly during endocytosis. Through reconstitution, we show that motors not only can pull out and extend protein-scaffolded tubes but also can cut them by FDS. FDS is generic, operating even in the absence of amphipathic helices in the BAR domain, and could in principle apply to any high-friction protein and membrane assembly.
Subject(s)
Endocytosis , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Acyltransferases/chemistry , Acyltransferases/metabolism , Animals , Biomechanical Phenomena , Friction , Humans , Lipid Metabolism , Protein Domains , RatsABSTRACT
Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux.
Subject(s)
Actins/immunology , Chemotaxis, Leukocyte/immunology , Lymphocyte Function-Associated Antigen-1/immunology , Receptors, CCR7/immunology , T-Lymphocytes/immunology , Actins/metabolism , Animals , Chemokines/immunology , Chemokines/metabolism , Friction , Integrins/immunology , Integrins/metabolism , Lymph Nodes , Lymphocyte Function-Associated Antigen-1/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, CCR7/metabolism , T-Lymphocytes/metabolismABSTRACT
Cytoskeletal remodeling is essential to eukaryotic cell division and morphogenesis. The mechanical forces driving the restructuring are attributed to the action of molecular motors and the dynamics of cytoskeletal filaments, which both consume chemical energy. By contrast, non-enzymatic filament crosslinkers are regarded as mere friction-generating entities. Here, we experimentally demonstrate that diffusible microtubule crosslinkers of the Ase1/PRC1/Map65 family generate directed microtubule sliding when confined between partially overlapping microtubules. The Ase1-generated forces, directly measured by optical tweezers to be in the piconewton-range, were sufficient to antagonize motor-protein driven microtubule sliding. Force generation is quantitatively explained by the entropic expansion of confined Ase1 molecules diffusing within the microtubule overlaps. The thermal motion of crosslinkers is thus harnessed to generate mechanical work analogous to compressed gas propelling a piston in a cylinder. As confinement of diffusible proteins is ubiquitous in cells, the associated entropic forces are likely of importance for cellular mechanics beyond cytoskeletal networks.
Subject(s)
Microtubules/metabolism , Animals , Biomechanical Phenomena , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Friction , Green Fluorescent Proteins/metabolism , Kinesins/metabolism , Microtubule-Associated Proteins/metabolism , Optical Tweezers , Schizosaccharomyces pombe Proteins/metabolismABSTRACT
The shape of cells is the outcome of the balance of inner forces produced by the actomyosin network and the resistive forces produced by cell adhesion to their environment. The specific contributions of contractile, anchoring and friction forces to network deformation rate and orientation are difficult to disentangle in living cells where they influence each other. Here, we reconstituted contractile actomyosin networks in vitro to study specifically the role of the friction forces between the network and its anchoring substrate. To modulate the magnitude and spatial distribution of friction forces, we used glass or lipids surface micropatterning to control the initial shape of the network. We adapted the concentration of Nucleating Promoting Factor on each surface to induce the assembly of actin networks of similar densities and compare the deformation of the network toward the centroid of the pattern shape upon myosin-induced contraction. We found that actin network deformation was faster and more coordinated on lipid bilayers than on glass, showing the resistance of friction to network contraction. To further study the role of the spatial distribution of these friction forces, we designed heterogeneous micropatterns made of glass and lipids. The deformation upon contraction was no longer symmetric but biased toward the region of higher friction. Furthermore, we showed that the pattern of friction could robustly drive network contraction and dominate the contribution of asymmetric distributions of myosins. Therefore, we demonstrate that during contraction, both the active and resistive forces are essential to direct the actin network deformation.
Subject(s)
Actins , Actomyosin , Friction , Muscle Contraction , Lipid BilayersABSTRACT
When described by a low-dimensional reaction coordinate, the folding rates of most proteins are determined by a subtle interplay between free-energy barriers, which separate folded and unfolded states, and friction. While it is commonplace to extract free-energy profiles from molecular trajectories, a direct evaluation of friction is far more elusive and typically relies on fits of measured reaction rates to memoryless reaction-rate theories. Here, using memory-kernel extraction methods founded on a generalized Langevin equation (GLE) formalism, we directly calculate the time-dependent friction acting on the fraction of native contacts reaction coordinate Q, evaluated for eight fast-folding proteins, taken from a published set of large-scale molecular dynamics protein simulations. Our results reveal that, across the diverse range of proteins represented in this dataset, friction is more influential than free-energy barriers in determining protein folding rates. We also show that proteins fold in a regime where the finite decay time of friction significantly reduces the folding times, in some instances by as much as a factor of 10, compared to predictions based on memoryless friction.
Subject(s)
Molecular Dynamics Simulation , Protein Folding , Friction , Proteins/metabolismSubject(s)
Lymphocyte Function-Associated Antigen-1 , T-Lymphocytes , Actins , Chemokines , FrictionABSTRACT
Until relatively recently, humans, similar to other animals, were habitually barefoot. Therefore, the soles of our feet were the only direct contact between the body and the ground when walking. There is indirect evidence that footwear such as sandals and moccasins were first invented within the past 40 thousand years1, the oldest recovered footwear dates to eight thousand years ago2 and inexpensive shoes with cushioned heels were not developed until the Industrial Revolution3. Because calluses-thickened and hardened areas of the epidermal layer of the skin-are the evolutionary solution to protecting the foot, we wondered whether they differ from shoes in maintaining tactile sensitivity during walking, especially at initial foot contact, to improve safety on surfaces that can be slippery, abrasive or otherwise injurious or uncomfortable. Here we show that, as expected, people from Kenya and the United States who frequently walk barefoot have thicker and harder calluses than those who typically use footwear. However, in contrast to shoes, callus thickness does not trade-off protection, measured as hardness and stiffness, for the ability to perceive tactile stimuli at frequencies experienced during walking. Additionally, unlike cushioned footwear, callus thickness does not affect how hard the feet strike the ground during walking, as indicated by impact forces. Along with providing protection and comfort at the cost of tactile sensitivity, cushioned footwear also lowers rates of loading at impact but increases force impulses, with unknown effects on the skeleton that merit future study.
Subject(s)
Callosities/physiopathology , Foot/pathology , Foot/physiology , Pain/physiopathology , Touch/physiology , Walking/physiology , Adult , Boston , Callosities/pathology , Female , Friction/physiology , Hardness/physiology , Humans , Kenya , Male , Middle Aged , Physical Stimulation , Pressure , Shoes , Skin Physiological Phenomena , Weight-Bearing/physiology , Young AdultABSTRACT
Many viruses eject their DNA via a nanochannel in the viral shell, driven by internal forces arising from the high-density genome packing. The speed of DNA exit is controlled by friction forces that limit the molecular mobility, but the nature of this friction is unknown. We introduce a method to probe the mobility of the tightly confined DNA by measuring DNA exit from phage phi29 capsids with optical tweezers. We measure extremely low initial exit velocity, a regime of exponentially increasing velocity, stochastic pausing that dominates the kinetics and large dynamic heterogeneity. Measurements with variable applied force provide evidence that the initial velocity is controlled by DNA-DNA sliding friction, consistent with a Frenkel-Kontorova model for nanoscale friction. We confirm several aspects of the ejection dynamics predicted by theoretical models. Features of the pausing suggest that it is connected to the phenomenon of 'clogging' in soft matter systems. Our results provide evidence that DNA-DNA friction and clogging control the DNA exit dynamics, but that this friction does not significantly affect DNA packaging.
Subject(s)
Bacteriophages , DNA, Viral , Viral Genome Packaging , Bacteriophages/genetics , DNA, Viral/genetics , Friction , Genome, Viral , KineticsABSTRACT
Legged movement is ubiquitous in nature and of increasing interest for robotics. Most legged animals routinely encounter foot slipping, yet detailed modeling of multiple contacts with slipping exceeds current simulation capacity. Here we present a principle that unifies multilegged walking (including that involving slipping) with slithering and Stokesian (low Reynolds number) swimming. We generated data-driven principally kinematic models of locomotion for walking in low-slip animals (Argentine ant, 4.7% slip ratio of slipping to total motion) and for high-slip robotic systems (BigANT hexapod, slip ratio 12 to 22%; Multipod robots ranging from 6 to 12 legs, slip ratio 40 to 100%). We found that principally kinematic models could explain much of the variability in body velocity and turning rate using body shape and could predict walking behaviors outside the training data. Most remarkably, walking was principally kinematic irrespective of leg number, foot slipping, and turning rate. We find that grounded walking, with or without slipping, is governed by principally kinematic equations of motion, functionally similar to frictional swimming and slithering. Geometric mechanics thus leads to a unified model for swimming, slithering, and walking. Such commonality may shed light on the evolutionary origins of animal locomotion control and offer new approaches for robotic locomotion and motion planning.
Subject(s)
Locomotion , Models, Biological , Walking , Animals , Biomechanical Phenomena , Foot , Friction , GaitABSTRACT
The origin of ice slipperiness has been a matter of great controversy for more than a century, but an atomistic understanding of ice friction is still lacking. Here, we perform computer simulations of an atomically smooth substrate sliding on ice. In a large temperature range between 230 and 266 K, hydrophobic sliders exhibit a premelting layer similar to that found at the ice/air interface. On the contrary, hydrophilic sliders show larger premelting and a strong increase of the first adsorption layer. The nonequilibrium simulations show that premelting films of barely one-nanometer thickness are sufficient to provide a lubricating quasi-liquid layer with rheological properties similar to bulk undercooled water. Upon shearing, the films display a pattern consistent with lubricating Couette flow, but the boundary conditions at the wall vary strongly with the substrate's interactions. Hydrophobic walls exhibit large slip, while hydrophilic walls obey stick boundary conditions with small negative slip. By compressing ice above atmospheric pressure, the lubricating layer grows continuously, and the rheological properties approach bulk-like behavior. Below 260 K, the equilibrium premelting films decrease significantly. However, a very large slip persists on the hydrophobic walls, while the increased friction on hydrophilic walls is sufficient to melt ice and create a lubrication layer in a few nanoseconds. Our results show that the atomic-scale frictional behavior of ice is a combination of spontaneous premelting, pressure melting, and frictional heating.
Subject(s)
Ice , Turtles , Animals , Friction , Lubrication , Motion Pictures , AdsorptionABSTRACT
Whether or not someone turns out to vote depends on their beliefs (such as partisanship or sense of civic duty) and on friction-external barriers such as long travel distance to the polls. In this exploratory study, we tested whether people underestimate the effect of friction on turnout and overestimate the effect of beliefs. We surveyed a representative sample of eligible US voters before and after the 2020 election (n = 1,280). Participants' perceptions consistently underemphasized friction and overemphasized beliefs (mean d = 0.94). In participants' open-text explanations, 91% of participants listed beliefs, compared with just 12% that listed friction. In contrast, turnout was shaped by beliefs only slightly more than friction. The actual belief-friction difference was about one-fourth the size of participants' perceptions (d = 0.24). This bias emerged across a range of survey measures (open- and close-ended; other- and self-judgments) and was implicated in downstream consequences such as support for friction-imposing policies and failing to plan one's vote.
Subject(s)
Culture , Politics , Social Perception , Friction , Humans , Models, Psychological , Power, Psychological , Surveys and Questionnaires , United StatesABSTRACT
The endosomal sorting complexes required for transport (ESCRT) system is an ancient and ubiquitous membrane scission machinery that catalyzes the budding and scission of membranes. ESCRT-mediated scission events, exemplified by those involved in the budding of HIV-1, are usually directed away from the cytosol ("reverse topology"), but they can also be directed toward the cytosol ("normal topology"). The ESCRT-III subunits CHMP1B and IST1 can coat and constrict positively curved membrane tubes, suggesting that these subunits could catalyze normal topology membrane severing. CHMP1B and IST1 bind and recruit the microtubule-severing AAA+ ATPase spastin, a close relative of VPS4, suggesting that spastin could have a VPS4-like role in normal-topology membrane scission. Here, we reconstituted the process in vitro using membrane nanotubes pulled from giant unilamellar vesicles using an optical trap in order to determine whether CHMP1B and IST1 are capable of membrane severing on their own or in concert with VPS4 or spastin. CHMP1B and IST1 copolymerize on membrane nanotubes, forming stable scaffolds that constrict the tubes, but do not, on their own, lead to scission. However, CHMP1B-IST1 scaffolded tubes were severed when an additional extensional force was applied, consistent with a friction-driven scission mechanism. We found that spastin colocalized with CHMP1B-enriched sites but did not disassemble the CHMP1B-IST1 coat from the membrane. VPS4 resolubilized CHMP1B and IST1 without leading to scission. These observations show that the CHMP1B-IST1 ESCRT-III combination is capable of severing membranes by a friction-driven mechanism that is independent of VPS4 and spastin.
Subject(s)
Cell Membrane , Endosomal Sorting Complexes Required for Transport , Oncogene Proteins , ATPases Associated with Diverse Cellular Activities/metabolism , Cell Membrane/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism , Friction , Humans , Oncogene Proteins/metabolism , Spastin/metabolism , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
When manipulating objects, humans begin adjusting their grip force to friction within 100 ms of contact. During motor adaptation, subjects become aware of the slipperiness of touched surfaces. Previously, we have demonstrated that humans cannot perceive frictional differences when surfaces are brought in contact with an immobilised finger, but can do so when there is submillimeter lateral displacement or subjects actively make the contact movement. Similarly, in, we investigated how humans perceive friction in the absence of intentional exploratory sliding or rubbing movements, to mimic object manipulation interactions. We used a two-alternative forced-choice paradigm in which subjects had to reach and touch one surface followed by another, and then indicate which felt more slippery. Subjects correctly identified the more slippery surface in 87 ± 8% of cases (mean ± SD; n = 12). Biomechanical analysis of finger pad skin displacement patterns revealed the presence of tiny (<1 mm) localised slips, known to be sufficient to perceive frictional differences. We tested whether these skin movements arise as a result of natural hand reaching kinematics. The task was repeated with the introduction of a hand support, eliminating the hand reaching movement and minimising fingertip movement deviations from a straight path. As a result, our subjects' performance significantly declined (66 ± 12% correct, mean ± SD; n = 12), suggesting that unrestricted reaching movement kinematics and factors such as physiological tremor, play a crucial role in enhancing or enabling friction perception upon initial contact. KEY POINTS: More slippery objects require a stronger grip to prevent them from slipping out of hands. Grip force adjustments to friction driven by tactile sensory signals are largely automatic and do not necessitate cognitive involvement; nevertheless, some associated awareness of grip surface slipperiness under such sensory conditions is present and helps to select a safe and appropriate movement plan. When gripping an object, tactile receptors provide frictional information without intentional rubbing or sliding fingers over the surface. However, we have discovered that submillimeter range lateral displacement might be required to enhance or enable friction sensing. The present study provides evidence that such small lateral movements causing localised partial slips arise and are an inherent part of natural reaching movement kinematics.
Subject(s)
Friction , Movement , Humans , Male , Biomechanical Phenomena , Adult , Female , Movement/physiology , Young Adult , Arm/physiology , Touch Perception/physiology , Fingers/physiology , Hand Strength/physiology , Touch/physiology , Psychomotor Performance/physiologyABSTRACT
Small-scale and flexible acoustic probes are more desirable for exquisite objects like human bodies and complex-shaped components than conventional rigid ones. Herein, a thin-film flexible acoustic sensor (FA-TES) that can detect ultra-broadband acoustic signals in multiple applications is proposed. The device consists of two thin copper-coated polyvinyl chloride films, which are stimulated by acoustic waves and contact each other to generate the triboelectric signal. Interlocking nanocolumn arrays fabricated on the friction surfaces are regarded as a highly adaptive spacer enabling this device to respond to ultra-broadband acoustic signals (100 Hz-4 MHz) and enhance sensor sensitivity for film weak vibration. Benefiting from the characteristics of high shape adaptability and ultrawide response range, the FA-TES can precisely sense human physiological sounds and voice (≤10 kHz) for laryngeal health monitoring and interaction in real-time. Moreover, the FA-TES flexibly arranged on a 3D-printed vertebra model can effectively and accurately diagnose the inner defect by ultrasonic testing (≥1 MHz). It envisions that this work can provide new ideas for flexible acoustic sensor designs and optimize real-time acoustic detections of human bodies and complex components.
Subject(s)
Acoustics , Ultrasonics , Humans , Ultrasonography , Sound , FrictionABSTRACT
To estimate object properties such as mass or friction, our brain relies on visual information to efficiently compute approximations. The role of sensorimotor feedback, however, is not well understood. Here we tested healthy adults (N = 79) in an inclined-plane problem, that is, how much a plane can be tilted before an object starts to slide, and contrasted the interaction group with observation groups who accessed involved forces by watching objects being manipulated. We created objects of different masses and levels of friction and asked participants to estimate the critical tilt angle after pushing an object, lifting it, or both. Estimates correlated with applied forces and were biased toward object mass, with higher estimates for heavier objects. Our findings highlight that inferences about physical object properties are tightly linked to the human sensorimotor system and that humans integrate sensorimotor information even at the risk of nonveridical perceptual estimates.
Subject(s)
Weight Perception , Adult , Humans , Friction , Brain , Psychomotor Performance , Hand StrengthABSTRACT
The friction of solids is primarily understood through the adhesive interactions between the surfaces. As a result, slick materials tend to be nonstick (e.g., Teflon), and sticky materials tend to produce high friction (e.g., tires and tape). Paradoxically, cartilage, the slippery bearing material of human joints, is also among the stickiest of known materials. This study aims to elucidate this apparent paradox. Cartilage is a biphasic material, and the most cited explanation is that both friction and adhesion increase as load transfers from the pressurized interstitial fluid to the solid matrix over time. In other words, cartilage is slippery and sticky under different times and conditions. This study challenges this explanation, demonstrating the strong adhesion of cartilage under high and low interstitial hydration conditions. Additionally, we find that cartilage clings to itself (a porous material) and Teflon (a nonstick material), as well as other surfaces. We conclude that the unusually strong interfacial tension produced by cartilage reflects suction (like a clingfish) rather than adhesion (like a gecko). This finding is surprising given its unusually large roughness, which typically allows for easy interfacial flow and defeats suction. The results provide compelling evidence that cartilage, like a clingfish, conforms to opposing surfaces and effectively seals submerged contacts. Further, we argue that interfacial sealing is itself a critical function, enabling cartilage to retain hydration, load support, and lubrication across long periods of inactivity.
Subject(s)
Cartilage, Articular , Cartilage, Articular/chemistry , Animals , Friction , Lubrication , Surface Properties , Adhesiveness , Polytetrafluoroethylene/chemistryABSTRACT
Nanotechnology has contributed important innovations to medicine and dentistry, and has also offered various applications to the field of orthodontics. Intraoral appliances must function in a complex environment that includes digestive enzymes, a diverse microbiome, mechanical stress, and fluctuations of pH and temperature. Nanotechnology can improve the performance of orthodontic brackets and archwires by reducing friction, inhibiting bacterial growth and biofilm formation, optimizing tooth remineralization, improving corrosion resistance and biocompatibility of metal substrates, and accelerating or decelerating orthodontic tooth movement through the application of novel nanocoatings, nanoelectromechanical systems, and nanorobots. This comprehensive review systematically explores the orthodontic applications of nanotechnology, particularly its impacts on tooth movement, antibacterial activity, friction reduction, and corrosion resistance. A search across PubMed, the Web of Science Core Collection, and Google Scholar yielded 261 papers, of which 28 met our inclusion criteria. These selected studies highlight the significant benefits of nanotechnology in orthodontic devices. Recent clinical trials demonstrate that advancements brought by nanotechnology may facilitate the future delivery of more effective and comfortable orthodontic care.
Subject(s)
Anti-Bacterial Agents , Friction , Nanotechnology , Orthodontics , Tooth Movement Techniques , Humans , Tooth Movement Techniques/instrumentation , Corrosion , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistryABSTRACT
In many physical networks, including neurons in the brain1,2, three-dimensional integrated circuits3 and underground hyphal networks4, the nodes and links are physical objects that cannot intersect or overlap with each other. To take this into account, non-crossing conditions can be imposed to constrain the geometry of networks, which consequently affects how they form, evolve and function. However, these constraints are not included in the theoretical frameworks that are currently used to characterize real networks5-7. Most tools for laying out networks are variants of the force-directed layout algorithm8,9-which assumes dimensionless nodes and links-and are therefore unable to reveal the geometry of densely packed physical networks. Here we develop a modelling framework that accounts for the physical sizes of nodes and links, allowing us to explore how non-crossing conditions affect the geometry of a network. For small link thicknesses, we observe a weakly interacting regime in which link crossings are avoided via local link rearrangements, without altering the overall geometry of the layout compared to the force-directed layout. Once the link thickness exceeds a threshold, a strongly interacting regime emerges in which multiple geometric quantities, such as the total link length and the link curvature, scale with the link thickness. We show that the crossover between the two regimes is driven by the non-crossing condition, which allows us to derive the transition point analytically and show that networks with large numbers of nodes will ultimately exist in the strongly interacting regime. We also find that networks in the weakly interacting regime display a solid-like response to stress, whereas in the strongly interacting regime they behave in a gel-like fashion. Networks in the weakly interacting regime are amenable to 3D printing and so can be used to visualize network geometry, and the strongly interacting regime provides insights into the scaling of the sizes of densely packed mammalian brains.
Subject(s)
Models, Structural , Nerve Net/anatomy & histology , Stress, Mechanical , Algorithms , Animals , Axons/physiology , Brain/anatomy & histology , Brain/cytology , Brain/physiology , Friction , Gels/chemistry , Mammals/anatomy & histology , Models, Biological , Nerve Net/cytology , Nerve Net/physiology , Printing, Three-DimensionalABSTRACT
Recent experiments by Brückner et al. [Science 380, 1357 (2023)] have observed an anomalous chain length dependence of the time of near approach of widely separated pairs of genomic elements on transcriptionally active chromosomal DNA. In this paper, I suggest that the anomaly may have its roots in internal friction between neighboring segments on the DNA backbone. The basis for this proposal is a model of chain dynamics formulated in terms of a continuum scaled Brownian walk (sBw) of polymerization index N. The sBw is an extension of the simple Brownian walk model widely used in path integral calculations of polymer properties, differing from it in containing an additional parameter H (the Hurst index) that can be tuned to produce varying degrees of correlation between adjacent monomers. A calculation using the sBw of the mean time τc for chain closure predicts-under the Wilemski-Fixman approximation for diffusion-controlled reactions-that at early times, τc varies as the 2/3 power of N, in close agreement with the findings of the Brückner et al. study. Other scaling relations of that study, including those related to the probability of loop formation and the mean square displacements of terminal monomers, are also satisfactorily accounted for by the model.