Photothermal therapies are based on the optical excitation of plasmonic nanoparticles in the biological environment. The effects of the irradiation on the biological medium depend critically on the ...heat transfer process at the nanoparticle interface, on the temperature reached by the tissues, as well as on the spatial extent of temperature gradients. Unfortunately, both the temperature and its biological effects are difficult to be probed experimentally at the molecular scale. Here, we approach this problem using nonequilibrium molecular dynamics simulations. We focus on photoporation, a photothermal application based on the irradiation of gold nanoparticles by single, short-duration laser pulses. The nanoparticles, stably bound to cell membranes, convert the radiation into heat, inducing transient changes of membrane permeability. We make a quantitative prediction of the temperature gradient around the nanoparticle upon irradiation by typical experimental laser fluences. Water permeability is locally enhanced around the nanoparticle, in an annular region that extends only a few nanometers from the nanoparticle interface. We correlate the local enhancement of permeability at the nanoparticle–lipid interface to the temperature inhomogeneities of the membrane and to the consequent availability of free volume pockets within the membrane core.
The rational design of supramolecular polymers that can adapt or respond in time to specific stimuli in a controlled way is interesting for many applications, but this requires understanding the ...molecular factors that make the material faster or slower in responding to the stimulus. To this end, it is necessary to study the dynamic adaptive properties at submolecular resolution, which is difficult at an experimental level. Here we show coarse-grained molecular dynamics simulations (<5 Å resolution) demonstrating how the dynamic adaptivity and stimuli responsiveness of a supramolecular polymer is controlled by the intrinsic dynamics of the assembly, which is in turn determined by the structure of the monomers. As a representative case, we focus on a water-soluble 1,3,5-benzenetricarboxamide (BTA) supramolecular polymer incorporating (charged) receptor monomers, experimentally seen to undergo dynamic clustering following the superselective binding to a multivalent recruiter. Our simulations show that the dynamic reorganization of the supramolecular structure proceeds via monomer diffusion on the dynamic fiber surface (exchange within the fiber). Rationally changing the structure of the monomers to make the fiber surface more or less dynamic allows tuning the rate of response to the stimulus and of supramolecular reconfiguration. Simple in silico experiments draw a structure–dynamics–property relationship revealing the key factors underpinning the dynamic adaptivity and stimuli-responsiveness of these supramolecular polymers. We come out with clear evidence that to master the bioinspired properties of these fibers, it is necessary to control their intrinsic dynamics, while the high-resolution of our molecular models permits us to show how.
Photothermal therapies are based on the optical excitation of plasmonic nanoparticles in the biological environment. The effects of the irradiation on the biological medium depend critically on the ...heat transfer process at the nanoparticle interface, on the temperature reached by the tissues as well as on the spatial extent of temperature gradients. Unfortunately, both the temperature and its biological effects are difficult to be probed experimentally at the molecular scale. Here, we approach this problem using nonequilibrium molecular dynamics simulations. We focus on photoporation, a photothermal application based on the irradiation of gold nanoparticles by single, short-duration laser pulses. The nanoparticles, stably bound to cell membranes, convert the radiation into heat, inducing transient changes of membrane permeability. We make a quantitative prediction of the temperature gradient around the nanoparticle upon irradiation by typical experimental laser fluences. Water permeability is locally enhanced around the NP, in an annular region that extends only a few nm far from the nanoparticle interface. We correlate the local enhancement of permeability at the NP-lipid interface to the temperature inhomogeneities of the membrane and to the consequent availability of free volume pockets within the membrane core.
Background: An inverse association between physical activity and metabolic syndrome has been reported in several cohorts, but very few specific studies are available in the elderly, in whom ...neurological and musculo-skeletal diseases are expected to lead to a remarkable age-related decline of physical activity. Aim and Design: The relationships among physical activity, insulin resistance and metabolic syndrome were assessed in a cross-sectional study concerning 1144 subjects aged 65–91 years resident in Pianoro (northern Italy). Household and leisure-time activities were assessed by a self-administered questionnaire (Physical Activity Scale for Elderly—PASE). Routine clinical and biochemical data (including fasting insulin) were used to assess insulin resistance Homeostasis Model Assessment (HOMA) method and the prevalence of metabolic syndrome. Results: All PASE scores were inversely correlated with waist circumference, triglycerides and HOMA index, with highest significance for leisure-time activities (P ⩽ 0.005). The PASE score for household activities was also correlated inversely with blood glucose (P < 0.05), and directly with HDL cholesterol (P < 0.001). In logistic regression analysis, the metabolic syndrome was more prevalent among sedentary subjects (corresponding to the low tertile of leisure-time activities) than in the remaining more active population (odds ratio 1.51, 95% confidence interval 1.12–2.03, P = 0.007), independently of possible confounders. Conclusion: Physical activity is inversely associated with insulin resistance and the metabolic syndrome even in the elderly. Community programs favoring physical activity are expected to significantly improve the health status in these subjects.
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