The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery ...of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0−0.6
mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (≥0.4
mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability.
Advancing age affects gait adaptability, but it is unclear if such adaptations to split-belt perturbations are already affected at middle-age. Changes in neuromuscular control, that already start at ...middle-age, may underlie the age-related changes in gait adaptation. Thus, we examined the effects of age on adaptations in gait and muscle activation patterns during split-belt walking in healthy young and middle-aged adults. Young (23.3 ± 3.13 years) and middle-aged adults (55.3 ± 2.91 years) walked on an instrumented split-belt treadmill. Both age groups adapted similarly by reducing asymmetry in step length and double support time. Surface EMG was recorded from eight leg muscles bilaterally. Principal Component Analysis (PCA) was applied to the EMG data of all subjects, for the fast and slow leg separately, to identify muscle activation patterns. The principal components consisted of i.e. temporal projections that were analyzed with Statistical Parametric Mapping (SPM). The functional muscle groups, identified by PCA, increased activation during early adaptation and post-adaptation, and decreased activation over time similarly in both age groups. Extra activation peaks of the plantar- and dorsiflexors suggest a role in gait modulation during split-belt walking. Both young and middle-aged adults re-established gait symmetry and showed adaptation effects in the muscle activation patterns. Since the adaptation of muscle activation patterns parallels adaptation of gait symmetry, changes in muscle activation likely underlie the changes in step parameters during split-belt adaptation. In conclusion, split-belt adaptation, in terms of gait and muscle activation patterns, is still preserved at middle-age, suggesting that age-related differences occur later in the lifespan.
The self-assembly process of clathrin coated pits during endocytosis has been simulated by combining and extending coarse grained models of the clathrin triskelion, the adaptor protein AP2, and a ...flexible network membrane. The AP2's core, upon binding to membrane and cargo, releases a motif that can bind clathrin. In conditions where the core-membrane-cargo binding is weak, the binding of this motif to clathrin can result in a stable complex. We characterize the conditions and mechanisms resulting in the formation of clathrin lattices that curve the membrane, i.e., clathrin coated pits. The mechanical properties of the AP2 β linker appear crucial to the orientation of the curved clathrin lattice relative to the membrane, with wild-type short linkers giving rise to the inward curving buds enabling endocytosis while long linkers produce upside-down cages and outward curving bulges.
Human bipedal gait requires active control of mediolateral dynamic balance to stay upright. The margin of stability is considered a measure of dynamic balance, and larger margins are by many authors ...assumed to reflect better balance control. The inverted pendulum model of gait indicates that changes in the mediolateral margin of stability are related to changes in bilateral single support times. We propose updated equations for the mediolateral margin of stability in temporally symmetric and asymmetric gait, which now include the single support times of both legs. Based on these equations, we study the relation between bilateral single support times and the mediolateral margin of stability in symmetric, asymmetric, and adaptive human gait. In all conditions, the mediolateral margin of stability during walking followed predictably from bilateral single support times, whereas foot placement co-varied less with the mediolateral margin of stability. Overall, these results demonstrate that the bilateral temporal regulation of gait profoundly affects the mediolateral margin of stability. By exploiting the passive dynamics of bipedal gait, bilateral temporal control may be an efficient mechanism to safeguard dynamic stability during walking, and keep an inherently unstable moving human body upright.
The ability to adapt dynamic balance to perturbations during gait deteriorates with age. To prevent age-related decline in adaptive control of dynamic balance, we must first understand how adaptive ...control of dynamic balance changes across the adult lifespan. We examined how adaptive control of the margin of stability (MoS) changes across the lifespan during perturbed and unperturbed walking on the split-belt treadmill.
Seventy-five healthy adults (age range, 18-80 yr) walked on an instrumented split-belt treadmill with and without split-belts. Linear regression analyses were performed for the mediolateral (ML) and anteroposterior (AP) MoS, step length, single support time, step width, double support time, and cadence during unperturbed and perturbed walking (split-belt perturbation), with age as predictor.
Age did not significantly affect dynamic balance during unperturbed walking. However, during perturbed walking, the ML MoS of the leg on the slow belt increased across the lifespan due to a decrease in bilateral single support time. The AP MoS did not change with aging despite a decrease in step length. Double support time decreased and cadence increased across the lifespan when adapting to split-belt walking. Age did not affect step width.
Aging affects the adaptive control of dynamic balance during perturbed but not unperturbed treadmill walking with controlled walking speed. The ML MoS increased across the lifespan, whereas bilateral single support times decreased. The lack of aging effects on unperturbed walking suggests that participants' balance should be challenged to assess aging effects during gait. The decrease in double support time and increase in cadence suggests that older adults use the increased cadence as a balance control strategy during challenging locomotor tasks.
Treadmills used for gait training in clinical rehabilitation and experimental settings are commonly fitted with handrails to assist or support persons in locomotor tasks. However, the effects of ...balance support through handrail holding on locomotor learning are unknown. Locomotor learning can be studied on split-belt treadmills, where participants walk on two parallel belts with asymmetric left and right belt speeds, to which they adapt their stepping pattern within a few minutes. The aim of this study was to determine how handrail holding affects the walking pattern during split-belt adaptation and after-effects in able-bodied persons. Fifty healthy young participants in five experimental groups were instructed to hold handrails, swing arms freely throughout the experiment or hold handrails during adaptation and swing arms freely during after-effects. Step length asymmetry and double support asymmetry were measured to assess the spatiotemporal walking pattern. The results showed that holding handrails during split-belt adaptation reduces magnitude of initial perturbation of step length asymmetry and reduces after-effects in step length asymmetry upon return to symmetric belt speeds. The findings of this study imply that balance support during gait training reduces locomotor learning, which should be considered in daily clinical gait practice and future research on locomotor learning.
•Frontal and sagittal plane margins of stability may covary.•This negative covariation may become critical during step lengthening.•We found covariation between margins of stability during normal ...walking.•There was no covariation during step lengthening.•Humans may increase step width to prevent critical lateral instability.
Control of dynamic balance in human walking is essential to remain stable and can be parameterized by the margins of stability. While frontal and sagittal plane margins of stability are often studied in parallel, they may covary, where increased stability in one plane could lead to decreased stability in the other. Hypothetically, this negative covariation may lead to critically low lateral stability during step lengthening.
Is there a relationship between frontal and sagittal plane margins of stability in able-bodied humans, during normal walking and imposed step lengthening?
Fifteen able-bodied adults walked on an instrumented treadmill in a normal walking and a step lengthening condition. During step lengthening, stepping targets were projected onto the treadmill in front of the participant to impose longer step lengths. Covariation between frontal and sagittal plane margins of stability was assessed with linear mixed-effects models for normal walking and step lengthening separately.
We found a negative covariation between frontal and sagittal plane margins of stability during normal walking, but not during step lengthening.
These results indicate that while a decrease in anterior instability may lead to a decrease in lateral stability during normal walking, able-bodied humans can prevent lateral instability due to this covariation in critical situations, such as step lengthening. These findings improve our understanding of adaptive dynamic balance control during walking in able-bodied humans and may be utilized in further research on gait stability in pathological and aging populations.
We simulate the linear and nonlinear rheology of two different viscoelastic polymer solutions, a polyisobutylene solution in pristane and an aqueous solution of hydroxypropylcellulose, using a highly ...coarse-grained approach known as Responsive Particle Dynamics (RaPiD) model. In RaPiD, each polymer has originally been depicted as a spherical particle with the effects of the eliminated degrees of freedom accounted for by an appropriate free energy and transient pairwise forces. Motivated by the inability of this spherical particle representation to entirely capture the nonlinear rheology of both fluids, we extended the RaPiD model by introducing a deformable particle capable of elongation. A Finite-Extensible Non-Linear Elastic potential provides a free energy penalty for particle elongation. Upon disentangling, this deformability allows more time for particles to re-entangle with neighbouring particles. We show this process to be integral towards recovering the experimental nonlinear rheology, obtaining excellent agreement. We show that the nonlinear rheology is crucially dependent upon the maximum elongation and less so on the elasticity of the particles. In addition, the description of the linear rheology has been retained in the process.
Dynamic balance control during human walking can be described by the distance between the mediolateral (ML) extrapolated center of mass (XCoM) position and the base of support, the margin of ...stability (MoS). The ML center of mass (CoM) position during treadmill walking can be estimated based on kinematic data (marker-based method) and a combination of ground reaction forces and center of pressure positions (GRF-based method). Here, we compare a GRF-based method with a full-body marker-based method for estimating the ML CoM, ML XCoM and ML MoS. Fifteen healthy adults walked on a dual-belt treadmill at comfortable walking speed for three minutes. Kinetic and kinematic data were collected and analyzed using a GRF-based and marker-based method to compare the ML CoM, ML XCoM and ML MoS. High correlation coefficients (r > 0.98) and small differences (Root Mean Square Difference < 0.0072 m) in ML CoM and ML XCoM were found between the GRF-based and marker-based methods. The GRF-based method resulted in larger ML XCoM excursion (0.0118 ± 0.0074 m) and smaller ML MoS values (0.0062 ± 0.0028 m) than the marker-based method, but these differences were consistent across participants. In conclusion, the GRF-based method is a valid method to determine the ML CoM, XCoM and MoS. One should be aware of higher ML XCoM and smaller ML MoS values in the GRF-based method when comparing absolute values between studies. The GRF-based method strongly reduces measurement times and can be used to provide real-time CoM-CoP feedback during treadmill gait training.
We investigate the shear-induced structure formation of colloidal particles dissolved in non-Newtonian fluids by means of computer simulations. The two investigated visco-elastic fluids are a ...semi-dilute polymer solution and a worm-like micellar solution. Both shear-thinning fluids contain long flexible chains whose entanglements appear and disappear continually as a result of Brownian motion and the applied shear flow. To reach sufficiently large time and length scales in three-dimensional simulations with up to 96 spherical colloids, we employ the responsive particle dynamics simulation method of modeling each chain as a single soft Brownian particle with slowly evolving inter-particle degrees of freedom accounting for the entanglements. Parameters in the model are chosen such that the simulated rheological properties of the fluids, i.e., the storage and loss moduli and the shear viscosities, are in reasonable agreement with experimental values. Spherical colloids dispersed in both quiescent fluids mix homogeneously. Under shear flow, however, the colloids in the micellar solution align to form strings in the flow direction, whereas the colloids in the polymer solution remain randomly distributed. These observations agree with recent experimental studies of colloids in the bulk of these two liquids.
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