48 research outputs found
Stability of heterogeneous parallel-bond adhesion clusters under static load
Adhesion interactions mediated by multiple bond types are relevant for many
biological and soft matter systems, including the adhesion of biological cells
and functionalized colloidal particles to various substrates. To elucidate
advantages and disadvantages of multiple bond populations for the stability of
heterogeneous adhesion clusters of receptor-ligand pairs, a theoretical model
for a homogeneous parallel adhesion bond cluster under constant loading is
extended to several bond types. The stability of the entire cluster can be
tuned by changing densities of different bond populations as well as their
extensional rigidity and binding properties. In particular, bond extensional
rigidities determine the distribution of total load to be shared between
different sub-populations. Under a gradual increase of the total load, the
rupture of a heterogeneous adhesion cluster can be thought of as a multistep
discrete process, in which one of the bond sub-populations ruptures first,
followed by similar rupture steps of other sub-populations or by immediate
detachment of the remaining cluster. This rupture behavior is qualitatively
independent of involved bond types, such as slip and catch bonds.
Interestingly, an optimal stability is generally achieved when the total
cluster load is shared such that loads on distinct bond populations are equal
to their individual critical rupture forces. We also show that cluster
heterogeneity can drastically affect cluster lifetime.Comment: 11 pages, 8 figure
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Interacting particles in an activity landscape
We study interacting active Brownian particles (ABPs) with a space-dependent swim velocity via simulation and theory. We find that, although an equation of state exists, a mechanical equilibrium does not apply to ABPs in activity landscapes. The pressure imbalance originates in the flux of polar order and the gradient of swim velocity across the interface between regions of different activity. An active-passive patch system is mainly controlled by the smallest global density for which the passive patch can be close packed. Below this density a critical point does not exist and the system splits continuously into a dense passive and a dilute active phase with increasing activity. Above this density and for sufficiently high activity the active phase may start to phase separate into a gas and a liquid phase caused by the same mechanism as motility-induced phase separation of ABPs with a homogeneous swim velocity
Interacting particles in an activity landscape
We study interacting active Brownian particles (ABPs) with a space-dependent
swim velocity via simulation and theory. We find that, although an equation of
state exists, a mechanical equilibrium does not apply to ABPs in activity
landscapes. The pressure difference originates in the flux of polar order and
the gradient of swim velocity across the interface between regions of different
activity. In contrast to motility-induced phase separation of ABPs with a
homogeneous swim velocity, a critical point does not exist for an
active-passive patch system, which continuously splits into a dense and a
dilute phase with increasing activity. However, if the global density is so
high that not all particles can be packed onto the inactive patch, then
MIPS-like behavior is restored and the pressure is balanced again.Comment: 12 pages, 5 figure
Fermeture de bulles de dénaturation de l'ADN couplées à l'élasticité de l'ADN
La compréhension physique des processus biologiques tels que la transcription nécessite de bien connaître la physique de l'ADN double brin. Une de ses propriétés thermodynamiques remarquable est sa dénaturation à une température particulière, lors de laquelle il se déroule et se sépare en deux brins après avoir formé des bulles (segments de paires de bases ouvertes consécutives). La dynamique de dénaturation jusqu'ici été étudiée l'échelle de la paire de base, ignorant ainsi les degrés de la chaîne. Ces études n'expliquent pas les temps de fermeture trés longs, de 20 s, mesurés par Alain-Bonnet et al.température ambiante pour des bulles de 18 paires de base. Dans cette thèse nous nous interessons la fermeture de grandes bulles de dénaturation thermalisées, l'aide de simulations de dynamique Brownienne d'un modèle simple "gros grains"de l'ADN. Nous montrons que la fermeture se fait en deux temps : d'abord, la bulle initiale se ferme rapidement jusqu'à ce qu'elle atteigne un état métastable, causé par les grandes énergies de courbure et de torsion emmagasinées dans la bulle. Ensuite, la fermeture de la bulle metastable se fait en fonction de la longueur de l'ADN et des parametres elastiques, soit apres la diffusion rotationnelle des "bras" rigides jusqu'à l'alignement de ceux-ci, soit lorsque la bulle a diffusée jusqu'un bout de la chaîne, ou soit localement lors d'une activation thermique. Nous montrons ainsi que le mécanisme physique associé des longs temps de fermeture est le couplage entre les degrés de liberté d'appariement et de conformations de l'ADN.The physical understainding of biological processes such as transcription requires the knowledge of double-stranded DNA (dsDNA) is its denaturation, at the melting temperature, in which it unwinds into two single-stranded DNAs via the formation of denaturation bubbles (segment of consecutive unpaired base-pairs). the dynamics of denaturation has beenstudies so far at the base-pair (bp) scale, ignoring conformational chaindegrees of freedom. These studies do not explain the very long closure times of 20 to 100µs, measured by atlan-Bonnet et al., of 18 bps long bubbles at room temperature. In this thesis, we study the closure of pre-equilibrated large bubbles, by using Brownian dynamics simulations of two simple DNA coarse-grained models. We show that the closure occurs via two steps : first, a fast zipping of the initial bubble occurs until a meta-stable state is reached, due to the large bending and twisting energies stored in the bubble. Then, the mete-stable bubble closes either via rotational diffusion of the stiff side arms until their alignment, or bubble diffusion until it reaches the chain end, or locally by thermal activation, depending on the DNA length and elastic moduli. We show that the physical mechanism behind these long timescales is therefore the dynamical coupling between base-pair and chain degrees of freedom
Acanthocyte Sedimentation Rate as a Diagnostic Biomarker for Neuroacanthocytosis Syndromes: Experimental Evidence and Physical Justification
(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases
among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs).
NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes.
Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to
misdiagnoses. (2) Methods: We measured the standard Westergren erythrocyte sedimentation
rate (ESR) of various blood samples from NAS patients and healthy controls. Furthermore, we
manipulated the ESR by swapping the erythrocytes and plasma of different individuals, as well
as replacing plasma with dextran. These measurements were complemented by clinical laboratory
data and single-cell adhesion force measurements. Additionally, we followed theoretical modeling
approaches. (3) Results: We show that the acanthocyte sedimentation rate (ASR) with a two-hour
read-out is significantly prolonged in chorea-acanthocytosis and McLeod syndrome without overlap
compared to the ESR of the controls. Mechanistically, through modern colloidal physics, we show
that acanthocyte aggregation and plasma fibrinogen levels slow down the sedimentation. Moreover,
the inverse of ASR correlates with the number of acanthocytes (R
2 = 0.61, p = 0.004). (4) Conclusions:
The ASR/ESR is a clear, robust and easily obtainable diagnostic marker. Independently of NASs, we
also regard this study as a hallmark of the physical view of erythrocyte sedimentation by describing
anticoagulated blood in stasis as a percolating gel, allowing the application of colloidal physics theory
The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib
Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification
Mesoscopic models for DNA stretching under force: new results and comparison to experiments
Single molecule experiments on B-DNA stretching have revealed one or two
structural transitions, when increasing the external force. They are
characterized by a sudden increase of DNA contour length and a decrease of the
bending rigidity. It has been proposed that the first transition, at forces of
60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA,
while the second one, at stronger forces, is a strand peeling resulting in
single stranded DNAs (ssDNA), similar to thermal denaturation. But due to
experimental conditions these two transitions can overlap, for instance for
poly(dA-dT). We derive analytical formula using a coupled discrete worm like
chain-Ising model. Our model takes into account bending rigidity, discreteness
of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit
of zero force, this model simplifies into a coupled model already developed by
us for studying thermal DNA melting, establishing a connexion with previous
fitting parameter values for denaturation profiles. We find that: (i) ssDNA is
fitted, using an analytical formula, over a nanoNewton range with only three
free parameters, the contour length, the bending modulus and the monomer size;
(ii) a surprisingly good fit on this force range is possible only by choosing a
monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase
length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss)
transitions; (iv) an analytical formula for fitting B to S transitions is
derived in the strong force approximation and for long DNAs, which is in
excellent agreement with exact transfer matrix calculations; (v) this formula
fits perfectly well poly(dG-dC) and -DNA force-extension curves with
consistent parameter values; (vi) a coherent picture, where S to ssDNA
transitions are much more sensitive to base-pair sequence than the B to S one,
emerges.Comment: 14 pages, 9 figure
DNA hybridization kinetics: zippering, internal displacement and sequence dependence
Although the thermodynamics of DNA hybridization is generally well established, the kinetics of this classic transition is less well understood. Providing such understanding has new urgency because DNA nanotechnology often depends critically on binding rates. Here, we explore DNA oligomer hybridization kinetics using a coarse-grained model. Strand association proceeds through a complex set of intermediate states, with successful binding events initiated by a few metastable base-pairing interactions, followed by zippering of the remaining bonds. But despite reasonably strong interstrand interactions, initial contacts frequently dissociate because typical configurations in which they form differ from typical states of similar enthalpy in the double-stranded equilibrium ensemble. Initial contacts must be stabilized by two or three base pairs before full zippering is likely, resulting in negative effective activation enthalpies. Non-Arrhenius behavior arises because the number of base pairs required for nucleation increases with temperature. In addition, we observe two alternative pathways—pseudoknot and inchworm internal displacement—through which misaligned duplexes can rearrange to form duplexes. These pathways accelerate hybridization. Our results explain why experimentally observed association rates of GC-rich oligomers are higher than rates of AT- rich equivalents, and more generally demonstrate how association rates can be modulated by sequence choice
Fermeture de bulles de dénaturation de l'ADN couplé à l'élasticité de l'ADN
The physical understanding of biological processes such as transcription requires the knowledge of double-stranded DNA (dsDNA) physics. A notable thermo- dynamic property of dsDNA is its denaturation, at the melting temperature, in which it unwinds into two single-stranded DNAs via the formation of denat- uration bubbles (segment of consecutive unpaired base-pairs). The dynamics of denaturation has been studied so far at the base-pair (bp) scale, ignoring conformational chain degrees of freedom. These studies do not explain the very long closure times of 20 to 100 s, measured by Altan-Bonnet et al., of 18 bps long bubbles at room temperature. In this thesis, we study the closure of pre-equilibrated large bubbles, by using Brownian dynamics simulations of two simple DNA coarse- grained models. We show that the closure occurs via two steps: rst, a fast zipping of the initial bubble occurs until a meta-stable state is reached, due to the large bending and twisting energies stored in the bubble. Then, the meta-stable bubble closes either via rotational di usion of the sti side arms until their alignment, or bubble di usion until it reaches the chain end, or locally by thermal activation, depending on the DNA length and elastic moduli. We show that the physical mechanism behind these long timescales is therefore the dynamical coupling between base-pair and chain degrees of freedom