28 research outputs found
Force-clamp experiments reveal the free energy profile and diffusion coefficient of the collapse of proteins
We present force-clamp data on the collapse of ubiquitin polyproteins in
response to a quench in the force. These nonequilibrium trajectories are
analyzed using a general method based on a diffusive assumption of the
end-to-end length to reconstruct a downhill free energy profile at 5pN and an
energy plateau at 10pN with a slow diffusion coefficient on the order
of~100nm^2/s. The shape of the free energy and its linear scaling with the
protein length give validity to a physical model for the collapse. However, the
length independent diffusion coefficient suggests that internal rather than
viscous friction dominates and thermal noise is needed to capture the
variability in the measured times to collapse.Comment: 12 pages, 4 figure
Biomimetic emulsions reveal the effect of homeostatic pressure on cell-cell adhesion
Cell-cell contacts in tissues are continuously subject to mechanical forces
due to homeostatic pressure and active cytoskeleton dynamics. While much is
known about the molecular pathways of adhesion, the role of mechanics is less
well understood. To isolate the role of pressure we present a dense packing of
functionalized emulsion droplets in which surface interactions are tuned to
mimic those of real cells. By visualizing the microstructure in 3D we find that
a threshold compression force is necessary to overcome electrostatic repulsion
and surface elasticity and establish protein-mediated adhesion. Varying the
droplet interaction potential maps out a phase diagram for adhesion as a
function of force and salt concentration. Remarkably, fitting the data with our
theoretical model predicts binder concentrations in the adhesion areas that are
similar to those found in real cells. Moreover, we quantify the adhesion size
dependence on the applied force and thus reveal adhesion strengthening with
increasing homeostatic pressure even in the absence of active cellular
processes. This biomimetic approach reveals the physical origin of
pressure-sensitive adhesion and its strength across cell-cell junctions.Comment: 20 pages, 5 figure
Evidence for marginal stability in emulsions
We report the first measurements of the effect of pressure on vibrational
modes in emulsions, which serve as a model for soft frictionless spheres at
zero temperature. As a function of the applied pressure, we find that the
density of states D(omega) exhibits a low-frequency cutoff omega*, which scales
linearly with the number of extra contacts per particle dz. Moreover, for
omega<omega*, D(omega)~ omega^2/omega*^2; a quadratic behavior whose prefactor
is larger than what is expected from Debye theory. This surprising result
agrees with recent theoretical findings. Finally, the degree of localization of
the softest low frequency modes increases with compression, as shown by the
participation ratio as well as their spatial configurations. Overall, our
observations show that emulsions are marginally stable and display
non-plane-wave modes up to vanishing frequencies
Colloidomers: freely-jointed polymers made of droplets
An important goal of self-assembly is to achieve a preprogrammed structure
with high fidelity. Here, we control the valence of DNA-functionalized
emulsions to make linear and branched model polymers, or `colloidomers'. The
distribution of cluster sizes is consistent with a polymerization process in
which the droplets achieve their prescribed valence. Conformational dynamics
reveals that the chains are freely-jointed, such that the end-to-end length
scales with the number of bonds as , where , in
agreement with the Flory theory in 2D. The chain diffusion coefficient
approximately scales as , as predicted by the Zimm model.
Unlike molecular polymers, colloidomers can be repeatedly assembled and
disassembled under temperature cycling, allowing for reconfigurable, responsive
matter
A Coarse-Grained Simulation Model for Self-Assembly of Liquid Droplets Featuring Explicit Mobile Binders
Colloidal particles with mobile binding molecules constitute a powerful
platform for probing the physics of self-assembly. Binding molecules are free
to diffuse and rearrange on the surface, giving rise to spontaneous control
over the number of droplet-droplet bonds, i.e., valence, as a function of the
concentration of binders. This type of valence control has been realized
experimentally by tuning the interaction strength between DNA-coated emulsion
droplets. Optimizing for valence two yields droplet polymer chains, termed
`colloidomers', which have recently been used to probe the physics of folding.
To understand the underlying self-assembly mechanisms, here we present a
coarse-grained molecular dynamics (CGMD) model to study the self-assembly of
this class of systems using explicit representations of mobile binding sites.
We explore how valence of assembled structures can be tuned through kinetic
control in the strong binding limit. More specifically, we optimize
experimental control parameters to obtain the highest yield of long linear
colloidomer chains. Subsequently tuning the dynamics of binding and unbinding
via a temperature-dependent model allows us to observe the heptamer chain
collapse into all possible rigid structures, in good agreement with recent
folding experiments. Our CGMD platform and dynamic bonding model (implemented
as an open-source custom plugin to HOOMD-Blue) reveal the molecular features
governing the binding patch size and valence control, and opens the study of
pathways in colloidomer folding. This model can therefore guide programmable
design in experiments.Comment: 14 pages + 11 pages SI. 10 figures + 9 supplemental figures + 6
supplemental table
Domain-domain interactions in Filamin A (16-23) impose a hierarchy of unfolding forces
The quaternary structure of Filamin A (FLNa) 16-23 was recently shown to
exhibit multiple domain-domain interactions that lead to a propeller-like
construction. Here we present single molecule force spectroscopy experiments to
show a wide variety of mechanical responses of this molecule and compare it
with its linear counterpart FLNa 1-8. The compact structure of FLNa 16-23 leads
to a broad distribution of rupture forces and end-to-end lengths in the
force-extension mode and multiple unraveling timescales in the force-clamp
mode. Moreover, a subset of force-extension trajectories reveals a mechanical
hierarchy in which the rupture of domain-domain interactions at high forces
(200 pN) liberates the unfolding of individual domains at low forces (100 pN).
This mechanism may also explain the order of magnitude difference in the rates
of the biexponential fits to the distribution of unfolding dwell times under
force-clamp. Overall, FLNa 16-23 under a force of 100 pN is more compliant than
the linear FLNa 1-8. Since a physiological role of FLNa is to crosslink actin
filaments, this range of responses allows it to accommodate a broad spectrum of
forces exerted by the cell and its environment
Model for random packing of polydisperse frictionless spheres
International audienceWe propose a statistical model for the random packing of frictionless polydisperse spheres in which the complexity of the global packing is distilled into a local stochastic process. We simplify the problem by considering the "granocentric" point of view of a single particle in the bulk, thereby reducing random packing to the assembly of nearest neighbours, followed by a random choice of contacts among them. The model is based on only two parameters, the available solid angle around each particle and the ratio of contacts to neighbors, which are both directly obtainable from experiments or simulations. As a result, the model analytically predicts the microscopic distributions of nearest neighbours and contacts, the local density fluctuations as well as the global density of the packing. We find that this granocentric view captures the essential properties of the polydisperse emulsion packing. This model suggests a general principle of organization for random packing and provides a statistical tool for quantifying the effect of the particle size distribution on the geometry of random packing in a variety of contexts of industrial relevance