43 research outputs found
Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells
Chemotaxis, the directional migration of cells in a chemical gradient, is robust to fluctuations associated with low chemical concentrations and dynamically changing gradients as well as high saturating chemical concentrations. Although a number of reports have identified cellular behavior consistent with a directional memory that could account for behavior in these complex environments, the quantitative and molecular details of such a memory process remain unknown. Using microfluidics to confine cellular motion to a 1D channel and control chemoattractant exposure, we observed directional memory in chemotactic neutrophil-like cells. We modeled this directional memory as a long-lived intracellular asymmetry that decays slower than observed membrane phospholipid signaling. Measurements of intracellular dynamics revealed that moesin at the cell rear is a long-lived element that when inhibited, results in a reduction of memory. Inhibition of ROCK (Rho-associated protein kinase), downstream of RhoA (Ras homolog gene family, member A), stabilized moesin and directional memory while depolymerization of microtubules (MTs) disoriented moesin deposition and also reduced directional memory. Our study reveals that long-lived polarized cytoskeletal structures, specifically moesin, actomyosin, and MTs, provide a directional memory in neutrophil-like cells even as they respond on short time scales to external chemical cues
Thermodynamic analysis of the Quantum Critical behavior of Ce-lattice compounds
A systematic analysis of low temperature magnetic phase diagrams of Ce
compounds is performed in order to recognize the thermodynamic conditions to be
fulfilled by those systems to reach a quantum critical regime and,
alternatively, to identify other kinds of low temperature behaviors. Based on
specific heat () and entropy () results, three different types of
phase diagrams are recognized: i) with the entropy involved into the ordered
phase () decreasing proportionally to the ordering temperature
(), ii) those showing a transference of degrees of freedom from the
ordered phase to a non-magnetic component, with their jump
() vanishing at finite temperature, and iii) those ending in a
critical point at finite temperature because their do not decrease
with producing an entropy accumulation at low temperature.
Only those systems belonging to the first case, i.e. with as
, can be regarded as candidates for quantum critical behavior.
Their magnetic phase boundaries deviate from the classical negative curvature
below \,K, denouncing frequent misleading extrapolations down to
T=0. Different characteristic concentrations are recognized and analyzed for
Ce-ligand alloyed systems. Particularly, a pre-critical region is identified,
where the nature of the magnetic transition undergoes significant
modifications, with its discontinuity strongly
affected by magnetic field and showing an increasing remnant entropy at . Physical constraints arising from the third law at are discussed
and recognized from experimental results
Antiferromagnetic spintronics
Antiferromagnetic materials are magnetic inside, however, the direction of
their ordered microscopic moments alternates between individual atomic sites.
The resulting zero net magnetic moment makes magnetism in antiferromagnets
invisible on the outside. It also implies that if information was stored in
antiferromagnetic moments it would be insensitive to disturbing external
magnetic fields, and the antiferromagnetic element would not affect
magnetically its neighbors no matter how densely the elements were arranged in
a device. The intrinsic high frequencies of antiferromagnetic dynamics
represent another property that makes antiferromagnets distinct from
ferromagnets. The outstanding question is how to efficiently manipulate and
detect the magnetic state of an antiferromagnet. In this article we give an
overview of recent works addressing this question. We also review studies
looking at merits of antiferromagnetic spintronics from a more general
perspective of spin-ransport, magnetization dynamics, and materials research,
and give a brief outlook of future research and applications of
antiferromagnetic spintronics.Comment: 13 pages, 7 figure
Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System
Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis
Persistent and polarised global actin flow is essential for directionality during cell migration
Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence
Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice
UK Medical Research Council Career Establishment Award (G0000170) to LS, MRC PhD Studentship Award to MJ (MR/J500380/1) and EU-FP7 Marie Curie ITN EpiTrain (REA grant agreement n° 316758) to SJM
Fibroblast Migration in 3D is Controlled by Haptotaxis in a Non-muscle Myosin II-Dependent Manner
Cell migration in 3D is a key process in many physiological and pathological processes. Although valuable knowledge has been accumulated through analysis of various 2D models, some of these insights are not directly applicable to migration in 3D. In this study, we have confined biomimetic hydrogels within microfluidic platforms in the presence of a chemoattractant (platelet-derived growth factor-BB). We have characterized the migratory responses of human fibroblasts within them, particularly focusing on the role of non-muscle myosin II. Our results indicate a prominent role for myosin II in the integration of chemotactic and haptotactic migratory responses of fibroblasts in 3D confined environments.Grants:
EUR/7FP/ERC-2012-StG 306751
ES/MINECO - DPI2012-38090-C03-01
ES/MINECO - SAF2011- 2495
Microfluidics: reframing biological enquiry
The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science