205 research outputs found
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
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
Power laws in microrheology experiments on living cells: comparative analysis and modelling
We compare and synthesize the results of two microrheological experiments on
the cytoskeleton of single cells. In the first one, the creep function J(t) of
a cell stretched between two glass plates is measured after applying a constant
force step. In the second one, a micrometric bead specifically bound to
transmembrane receptors is driven by an oscillating optical trap, and the
viscoelastic coefficient is retrieved. Both and
exhibit power law behavior: and , with the same exponent
. This power law behavior is very robust ; is
distributed over a narrow range, and shows almost no dependance on the cell
type, on the nature of the protein complex which transmits the mechanical
stress, nor on the typical length scale of the experiment. On the contrary, the
prefactors and appear very sensitive to these parameters. Whereas
the exponents are normally distributed over the cell population, the
prefactors and follow a log-normal repartition. These results are
compared with other data published in the litterature. We propose a global
interpretation, based on a semi-phenomenological model, which involves a broad
distribution of relaxation times in the system. The model predicts the power
law behavior and the statistical repartition of the mechanical parameters, as
experimentally observed for the cells. Moreover, it leads to an estimate of the
largest response time in the cytoskeletal network: s.Comment: 47 pages, 14 figures // v2: PDF file is now Acrobat Reader 4 (and up)
compatible // v3: Minor typos corrected - The presentation of the model have
been substantially rewritten (p. 17-18), in order to give more details -
Enhanced description of protocols // v4: Minor corrections in the text : the
immersion angles are estimated and not measured // v5: Minor typos corrected.
Two references were clarifie
Neutral and Charged Polymers at Interfaces
Chain-like macromolecules (polymers) show characteristic adsorption
properties due to their flexibility and internal degrees of freedom, when
attracted to surfaces and interfaces. In this review we discuss concepts and
features that are relevant to the adsorption of neutral and charged polymers at
equilibrium, including the type of polymer/surface interaction, the solvent
quality, the characteristics of the surface, and the polymer structure. We pay
special attention to the case of charged polymers (polyelectrolytes) that have
a special importance due to their water solubility. We present a summary of
recent progress in this rapidly evolving field. Because many experimental
studies are performed with rather stiff biopolymers, we discuss in detail the
case of semi-flexible polymers in addition to flexible ones. We first review
the behavior of neutral and charged chains in solution. Then, the adsorption of
a single polymer chain is considered. Next, the adsorption and depletion
processes in the many-chain case are reviewed. Profiles, changes in the surface
tension and polymer surface excess are presented. Mean-field and corrections
due to fluctuations and lateral correlations are discussed. The force of
interaction between two adsorbed layers, which is important in understanding
colloidal stability, is characterized. The behavior of grafted polymers is also
reviewed, both for neutral and charged polymer brushes.Comment: a review: 130 pages, 30 ps figures; final form, added reference
Association of cetuximab with adverse pulmonary events in cancer patients: a comprehensive review
Compounds derived from biologic sources, or biologicals, are increasingly utilized as therapeutic agents in malignancy. Development of anti-cancer targeted therapies from biologics is increasingly being utilized. Cetuximab, a chimeric monoclonal antibody, is one such anti-cancer targeted therapeutic that has shown efficacy in quelling the rate of patient decline in colorectal, head/neck, and non-small cell lung cancer. However, due to the relatively recent addition of biologic compounds to the therapeutic arsenal, information related to adverse reactions is less well known than those seen in traditional chemotherapeutics. Dermatologic reactions have been demonstrated as the most frequent side effect cited during cetuximab therapy for malignancy; however, other effects may lead to greater morbidity. In general, pulmonary complications of therapeutics can lead to significant morbidity and mortality. The purpose of this review is to compile the various pulmonary side effects seen in patients treated with cetuximab for various malignancies, and to compare the incidence of these adverse reactions to standard therapies
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