32 research outputs found
Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia
Diverse molecules induce general anesthesia with potency strongly correlated with both their hydrophobicity and their effects on certain ion channels. We recently observed that several n -alcohol anesthetics inhibit heterogeneity in plasma-membrane-derived vesicles by lowering the critical temperature (Tc) for phase separation. Here, we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n -alcohols and effects on Tc. First, we show that hexadecanol acts oppositely to n -alcohol anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described âintoxication reversersâ raise Tc and counter ethanolâs effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that elevated hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that ÎTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia
Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting
We present an analytical method to quantify clustering in super-resolution
localization images of static surfaces in two dimensions. The method also
describes how over-counting of labeled molecules contributes to apparent
self-clustering and how the effective lateral resolution of an image can be
determined. This treatment applies to clustering of proteins and lipids in
membranes, where there is significant interest in using super-resolution
localization techniques to probe membrane heterogeneity. When images are
quantified using pair correlation functions, the magnitude of apparent
clustering due to over-counting will vary inversely with the surface density of
labeled molecules and does not depend on the number of times an average
molecule is counted. Over-counting does not yield apparent co-clustering in
double label experiments when pair cross-correlation functions are measured. We
apply our analytical method to quantify the distribution of the IgE receptor
(Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells
from images acquired using stochastic optical reconstruction microscopy (STORM)
and scanning electron microscopy (SEM). We find that apparent clustering of
labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from
over-counting of individual complexes. Thus our results indicate that these
receptors are randomly distributed within the resolution and sensitivity limits
of these experiments.Comment: 22 pages, 5 figure
Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness
<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p>
<b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p>
<b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts
Nonadditivity of critical Casimir forces
In soft condensed matter physics, effective interactions often emerge due to the spatial confinement of fluctuating fields. For instance, microscopic particles dissolved in a binary liquid mixture are subject to critical Casimir forces whenever their surfaces confine the thermal fluctuations of the order parameter of the solvent close to its critical demixing point. These forces are theoretically predicted to be nonadditive on the scale set by the bulk correlation length of the fluctuations. Here we provide direct experimental evidence of this fact by reporting the measurement of the associated many-body forces. We consider three colloidal particles in optical traps and observe that the critical Casimir force exerted on one of them by the other two differs from the sum of the forces they exert separately. This three-body effect depends sensitively on the distance from the critical point and on the chemical functionalisation of the colloid surfaces
Membrane-mediated interactions
Interactions mediated by the cell membrane between inclusions, such as
membrane proteins or antimicrobial peptides, play important roles in their
biological activity. They also constitute a fascinating challenge for
physicists, since they test the boundaries of our understanding of
self-assembled lipid membranes, which are remarkable examples of
two-dimensional complex fluids. Inclusions can couple to various degrees of
freedom of the membrane, resulting in different types of interactions. In this
chapter, we review the membrane-mediated interactions that arise from direct
constraints imposed by inclusions on the shape of the membrane. These effects
are generic and do not depend on specific chemical interactions. Hence, they
can be studied using coarse-grained soft matter descriptions. We deal with
long-range membrane-mediated interactions due to the constraints imposed by
inclusions on membrane curvature and on its fluctuations. We also discuss the
shorter-range interactions that arise from the constraints on membrane
thickness imposed by inclusions presenting a hydrophobic mismatch with the
membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens
P. (eds) Physics of Biological Membranes. Springer, Cha