Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria - via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces - results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm.

The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal microscopy, we establish that these membrane deformations cause an attractive interaction force leading to reversible binding. The attraction extends over 2.5 times the particle diameter and has a strength of three times the thermal energy (-3.3 k_BT). Coarse-grained Monte-Carlo simulations of the system are in excellent agreement with the experimental results and prove that the measured interaction is independent of length scale. Our combined experimental and numerical results reveal membrane curvature as a common physical origin for interactions between any membrane-deforming objects, from nanometre-sized proteins to micrometre-sized particles.

Membrane tubes and tubular networks are ubiquitous in living cells. Inclusions like proteins are vital for both the stability and the dynamics of such networks. These inclusions interact via the curvature deformations they impose on the membrane. We analytically study the resulting membrane mediated interactions in strongly curved tubular membranes. We model inclusions as constraints coupled to the curvature tensor of the membrane tube. First, as special test cases, we analyze the interaction between ring- and rod-shaped inclusions. Using Monte Carlo simulations, we further show how pointlike inclusions interact to form linear aggregates. To minimize the curvature energy of the membrane, inclusions self-assemble into either line- or ringlike patterns. Our results show that the global curvature of the membrane strongly affects the interactions between proteins embedded in it, and can lead to the spontaneous formation of biologically relevant structures.

Inclusions in biological membranes may interact via deformations they induce on the shape of that very membrane. Such deformations are a purely physical effect, resulting in nonspecific forces between the inclusions. In this Letter we show that this type of interaction can organize membrane domains and hence may play an important biological role. Using a simple analytical model we predict that membrane inclusions sort according to the curvature they impose. We verify this prediction by both numerical simulations and experimental observations of membrane domains in phase separated vesicles.

Collections of motors dynamically organize to extract membrane tubes. These tubes grow but often pause or change direction as they traverse an underlying microtubule (MT) network. In vitro, membrane tubes also stall: they stop growing in length despite a large group of motors available at the tip to pull them forward. In these stationary membrane tubes in vitro, we find that clusters of processive kinesin motors form and reach the tip of the tube at regular time intervals. The average times between cluster arrivals depends on the time over which motors depart from the tip, suggesting that motors are recycled toward the tip. Numerical simulations of the motor dynamics in the membrane tube and on the MTs show that the presence of cooperative binding between motors quantitatively accounts for the clustering observed experimentally. Cooperative binding along the length of the MT and a nucleation point at a distance behind the tip define the recycling period. Based on comparison of the numerical results and experimental data, we estimate a cooperative binding probability and concentration regime where the recycling phenomenon occurs.

Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors. When two cells touch, an adhesion link is created between them by means of transmembrane E-cadherin proteins. Simultaneously, their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links. Here, we propose a detailed quantitative model of the role of cytoplasmic β-catenin and a-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact the concentration in α-catenin dinners increases, inhibiting actin branching and thereby reducing cellular motility and expansion pressure. This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin, β-catenin, and α-catenin in the cellular phenotype and in tumorigenesis. In particular, we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene. Potential direct tests of our model are discussed.

Cell membrane organization is the result of the collective effect of many driving forces. Several of these, such as electrostatic and van der Waals forces, have been identified and studied in detail. In this article, we investigate and quantify another force, the interaction between inclusions via deformations of the membrane shape. For electrically neutral systems, this interaction is the dominant organizing force. As a model system to study membrane-mediated interactions, we use phase-separated biomimetic vesicles that exhibit coexistence of liquid-ordered and liquid-disordered lipid domains. The membrane-mediated interactions between these domains lead to a rich variety of effects, including the creation of long-range order and the setting of a preferred domain size. Our findings also apply to the interaction of membrane protein patches, which induce similar membrane shape deformations and hence experience similar interactions.

Heterogeneities in the cell membrane due to coexisting lipid phases have been conjectured to play a major functional role in cell signaling and membrane trafficking. Thereby the material properties of multiphase systems, such as the line tension and the bending moduli, are crucially involved in the kinetics and the asymptotic behavior of phase separation. In this Letter we present a combined analytical and experimental approach to determine the properties of phase-separated vesicle systems. First we develop an analytical model for the vesicle shape of weakly budded biphasic vesicles. Subsequently experimental data on vesicle shape and membrane fluctuations are taken and compared to the model. The parameters obtained set limits for the size and stability of nanodomains in the plasma membrane of living cells.