Abstract The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well-defined elasticity, size and surface coating enable internalization within cellular environment. By isotropically compressing multicellular...

The extent, mechanism, and function of cell volume changes during specific cellular events, such as migration division, have been poorly studied, mostly because a lack adequate techniques. Here we unambiguously report that large range mammalian types display significant increase in mitosis (up to 30%). We further show this is tightly linked the mitotic state not its spread or rounded shape independent presence an intact actomyosin cortex. Importantly, accompanied by dry mass thus corresponds...

The elucidation of physical and molecular mechanisms by which a membrane tube is generated from reservoir central to the understanding structure dynamics intracellular organelles transport intermediates in eukaryotic cells. Compelling evidence exists that motors dynein kinesin families are involved tubulation organelles. Here, we show lipid giant unilamellar vesicles (GUVs), molecules have been attached means small polystyrene beads, give rise tubes complex tubular networks when incubated...

The precise role of the microenvironment on tumor growth is poorly understood. Whereas in constant competition with surrounding tissue, little known about mechanics this interaction. Using a novel experimental procedure, we study quantitatively effect an applied mechanical stress long-term spheroid cell aggregate. We observe that 10 kPa sufficient to drastically reduce by inhibition proliferation mainly core spheroid. compare results simple numerical model developed describe cancer progression.

In most instances, tumors have to push their surroundings in order grow. Thus, during development, must be able both exert and sustain mechanical stresses. Using a novel experimental procedure, we study quantitatively the effect of an applied stress on long-term growth spherical cell aggregate. Our results indicate possibility modulate tumor depending pressure. Moreover, demonstrate that cells located core spheroid display different response than those periphery. We compare simple numerical...

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both normal pathological conditions. To perceive mechanical perturbations of different types magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results selective osmotic compressions CT26 mouse cells within multicellular aggregates global aggregate compressions, we show have strong impact on growth internal cell motility, while same...

The structural and functional organization of biological tissues relies on the intricate interplay between chemical mechanical signaling. Whereas role constant transient perturbations is generally accepted, several studies recently highlighted existence long-range excitations (i.e., waves) at supracellular level. Here, we confine epithelial cell monolayers to quasi-one-dimensional geometries, force establishment tissue-level waves well-defined wavelength period. Numerical simulations based a...

We observe the myosin V stepping mechanism by traveling wave tracking. This technique, associated with optical tweezers, allows one to follow a scattering particle in two-dimensional plane, nanometer accuracy and temporal resolution microsecond range. have observed that, at millisecond time scale, combines longitudinal vertical motions during step. Because this scale steps appear heterogeneous, we deduce their general features aligning averaging large number of them. Our data show that 36-nm...

Human Rad51 (hRad51), the protein central to DNA pairing and strand exchange during homologous recombination, polymerizes on form nucleoprotein filaments. By making use of magnetic tweezers manipulate individual molecules, we measured nucleation growth hRad51 filaments, their subsequent disassembly in real time. The dependence initial polymerization rate upon concentration suggests that rate-limiting step is formation a nucleus involving 5.5 +/- 1.5 monomers, corresponding one helical turn...

Collective cell motion is observed in a wide range of biological processes. In tumors, physiological gradients nutrients, growth factors, or even oxygen give rise to proliferation. We show using fluorescently labeled particles that these drive velocity field resulting cellular flow multicellular spheroids. Under mechanical stress, the drastically reduced. describe results with hydrodynamic model considers only convection by flow.

Abstract The mechanical properties of biological tissues are key to their physical integrity and function. Although external loading or biochemical treatments allow the estimation these globally, it remains difficult assess how such stimuli compare with cell-generated contractions. Here we engineer microtissues composed optogenetically-modified fibroblasts encapsulated within collagen. Using light control activity RhoA, a major regulator cellular contractility, induce local contractions...

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially epithelial tissues with strong cell–cell adhesion. However, quantitative description transmission chain from force generation sender cell, propagation across boundaries, concomitant response receiver cells is missing. For analysis...

Molecular motors often work collectively inside the cell. While properties of individual have been extensively studied over last decade, much less is known on how coordinate their action when working in ensembles. The motor collective behaviour conditions where they contact each other, as intracellular transport, may strongly depend mutual interactions. In particular, interactions result clustering without need additional proteins. Here we study between kinesin-1 molecules by analysing...

Cell contraction and proliferation, matrix secretion external mechanical forces induce compression during embryogenesis tumor growth, which in turn regulate cell metabolism or differentiation. How affects tissue contractility, a hallmark of function, is however unknown. Here we apply osmotic to microtissues either mouse colon adenocarcinoma CT26 cells, NIH 3T3 fibroblasts, human primary cancer-associated fibroblasts. Microtissues are anchored flexible pillars that serve as force transducers....

The human recombinase hRad51 is a key protein for the maintenance of genome integrity and cancer development. Polymerization depolymerization on duplex DNA were studied here using new generation magnetic tweezers, measuring twist in real time with resolution 5 degrees . Our results combined earlier structural information suggest that somewhat less extended by than RecA (4.5 vs. 5.1 A per base pair) untwisted 18.2 pair. They also confirm stoichiometry 3-4 bp hRad51-dsDNA nucleoprotein...

Tumors are subjected to mechanical stress generated by their own growth in a confined environment, and surrounding tissues. Recent works have focused on the study of spherical aggregates cells, spheroids, under controlled confinement or stress. In this we demonstrate measurement spatially temporally resolved deformation maps inside spheroids while applying an osmo-mechanical We use full field optical coherence tomography, high resolution imaging technique well suited for real-time...

In eukaryotes, Rad51 protein is responsible for the recombinational repair of double-strand DNA breaks. monomers cooperatively assemble on exonuclease-processed broken ends forming helical nucleo-protein filaments that can pair with homologous regions sister chromatids. Homologous pairing allows to be reunited in a complex but error-free process. has ATPase activity its role poorly understood, as independent adenosine triphosphate (ATP) hydrolysis. Here we use magnetic tweezers and electron...

We study the motion of kinesin molecular motor along microtubules using interference total internal reflection microscopy. This technique achieves nanometer scale resolution together with a fast time response. describe first in vitro observation stepping at high ATP concentration absence an external load, where 8-nm step can be clearly distinguished. The short-time allows us to measure constant related relative bead-motor connection; we deduce associated elastic modulus.