100 research outputs found
Hysteresis in the cell response to time-dependent substrate stiffness
Mechanical cues like the rigidity of the substrate are main determinants for
the decision making of adherent cells. Here we use a mechano-chemical model to
predict the cellular response to varying substrate stiffness. The model
equations combine the mechanics of contractile actin filament bundles with a
model for the Rho-signaling pathway triggered by forces at cell-matrix
contacts. A bifurcation analysis of cellular contractility as a function of
substrate stiffness reveals a bistable response, thus defining a lower
threshold of stiffness, below which cells are not able to build up contractile
forces, and an upper threshold of stiffness, above which cells are always in a
strongly contracted state. Using the full dynamical model, we predict that
rate-dependent hysteresis will occur in the cellular traction forces when cells
are exposed to substrates of time-dependent stiffness.Comment: Revtex, 4 PDF figure
Collective dynamics of actomyosin cortex endow cells with intrinsic mechanosensing properties
Living cells adapt and respond actively to the mechanical properties of their
environment. In addition to biochemical mechanotransduction, evidence exists
for a myosin-dependent, purely mechanical sensitivity to the stiffness of the
surroundings at the scale of the whole cell. Using a minimal model of the
dynamics of actomyosin cortex, we show that the interplay of myosin power
strokes with the rapidly remodelling actin network results in a regulation of
force and cell shape that adapts to the stiffness of the environment.
Instantaneous changes of the environment stiffness are found to trigger an
intrinsic mechanical response of the actomyosin cortex. Cortical retrograde
flow resulting from actin polymerisation at the edges is shown to be modulated
by the stress resulting from myosin contractility, which in turn regulates the
cell size in a force-dependent manner. The model describes the maximum force
that cells can exert and the maximum speed at which they can contract, which
are measured experimentally. These limiting cases are found to be associated
with energy dissipation phenomena which are of the same nature as those taking
place during the contraction of a whole muscle. This explains the fact that
single nonmuscle cell and whole muscle contraction both follow a Hill-like
force-velocity relationship
Rigidity sensing explained by active matter theory
The magnitude of traction forces exerted by living animal cells on their
environment is a monotonically increasing and approximately sigmoidal function
of the stiffness of the external medium. This observation is rationalized using
active matter theory: adaptation to substrate rigidity results from an
interplay between passive elasticity and active contractility.Comment: 4 pages, 2 figure
How the cell got its shape : A visco-elasto-active model of the cytoskeleton
Living cells cytoskeleton is made of polymers which are constantly being re-modelled by polymerisation and depolymerisation, and which are bound to one another (crosslinked) through even more unstable molecules, lasting for about one second. With such a dynamic structure, one may wonder how cells can maintain a given shape over time ranges several orders of magnitude larger than the turn-over time of their constituents. We propose a rheological model which features crosslink turn-over, polymerisation and molecular motor-generated contractile forces, and provides answers to these questions
Instabilities and Oscillations in Isotropic Active Gels
We present a generic formulation of the continuum elasticity of an isotropic
crosslinked active gel. The gel is described by a two-component model
consisting of an elastic network coupled frictionally to a permeating fluid.
Activity is induced by active crosslinkers that undergo an ATP-activated cycle
and transmit forces to the network. The on/off dynamics of the active
crosslinkers is described via rate equations for unbound and bound motors. For
large activity motors yield a contractile instability of the network. At
smaller values of activity, the on/off motor dynamics provides an effective
inertial drag on the network that opposes elastic restoring forces, resulting
in spontaneous oscillations. Our work provides a continuum formulation that
unifies earlier microscopic models of oscillations in muscle sarcomeres and a
generic framework for the description of the large scale properties of
isotropic active solids.Comment: 13 pages, 5 figure
Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks
Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells
Force Generation upon T Cell Receptor Engagement
T cells are major players of adaptive immune response in mammals. Recognition of
an antigenic peptide in association with the major histocompatibility complex at
the surface of an antigen presenting cell (APC) is a specific and sensitive
process whose mechanism is not fully understood. The potential contribution of
mechanical forces in the T cell activation process is increasingly debated,
although these forces are scarcely defined and hold only limited experimental
evidence. In this work, we have implemented a biomembrane force probe (BFP)
setup and a model APC to explore the nature and the characteristics of the
mechanical forces potentially generated upon engagement of the T cell receptor
(TCR) and/or lymphocyte function-associated antigen-1 (LFA-1). We show that upon
contact with a model APC coated with antibodies towards TCR-CD3, after a short
latency, the T cell developed a timed sequence of pushing and pulling forces
against its target. These processes were defined by their initial constant
growth velocity and loading rate (force increase per unit of time). LFA-1
engagement together with TCR-CD3 reduced the growing speed during the pushing
phase without triggering the same mechanical behavior when engaged alone.
Intracellular Ca2+ concentration
([Ca2+]i) was monitored simultaneously
to verify the cell commitment in the activation process.
[Ca2+]i increased a few tens of seconds
after the beginning of the pushing phase although no strong correlation appeared
between the two events. The pushing phase was driven by actin polymerization.
Tuning the BFP mechanical properties, we could show that the loading rate during
the pulling phase increased with the target stiffness. This indicated that a
mechanosensing mechanism is implemented in the early steps of the activation
process. We provide here the first quantified description of force generation
sequence upon local bidimensional engagement of TCR-CD3 and discuss its
potential role in a T cell mechanically-regulated activation process
Contour models of cellular adhesion
The development of traction-force microscopy, in the past two decades, has
created the unprecedented opportunity of performing direct mechanical
measurements on living cells as they adhere or crawl on uniform or
micro-patterned substrates. Simultaneously, this has created the demand for a
theoretical framework able to decipher the experimental observations, shed
light on the complex biomechanical processes that govern the interaction
between the cell and the extracellular matrix and offer testable predictions.
Contour models of cellular adhesion, represent one of the simplest and yet most
insightful approach in this problem. Rooted in the paradigm of active matter,
these models allow to explicitly determine the shape of the cell edge and
calculate the traction forces experienced by the substrate, starting from the
internal and peripheral contractile stresses as well as the passive restoring
forces and bending moments arising within the actin cortex and the plasma
membrane. In this chapter I provide a general overview of contour models of
cellular adhesion and review the specific cases of cells equipped with
isotropic and anisotropic actin cytoskeleton as well as the role of bending
elasticity.Comment: 24 pages, 9 figures. arXiv admin note: text overlap with
arXiv:1304.107
Acto-myosin based response to stiffness and rigidity sensing
Cells sense the rigidity of their environment and respond to it. Most studies have been focused on the role of adhesion complexes in rigidity sensing. In particular, it has been clearly shown that proteins of the adhesion complexes were stretch-sensitive and could thus trigger mechano-chemical signaling in response to applied forces. In order to understand how this local mechano-sensitivity could be coordinated at the cell scale, we have recently carried out single cell traction force measurements on springs of varying stiffness. We found that contractility at the cell scale (force, speed of contraction, mechanical power) was indeed adapted to external stiffness and reflected ATPase activity of non-muscle myosin II and acto-myosin response to load. Here we suggest a scenario of rigidity sensing where local adhesions sensitivity to force could be coordinated by adaptation of the acto-myosin dependent cortical tension at the global cell scale. Such a scenario could explain how spreading and migration are oriented by the rigidity of the cell environment
DEVELOPMENTAL CHARACTERISTICS OF HISTAMINE METHYLTRANSFERASE AND PHENYLETHANOLAMINE-N-METHYL-TRANSFERASE OF RAT-BRAIN
- …