Once in biological fluids, the surface of nanoparticles (NPs) is rapidly covered with a layer of biomolecules (i.e., the “protein corona”) whose composition strongly determines their biological identity, regulates interactions with biological entities including cells and the immune system, and consequently directs the biological fate and pharmacokinetics of nanoparticles. We recently introduced the concept of a “personalized protein corona” which refers to the formation of different biological identities of the exact same type of NP after being exposed to extract plasmas from individuals who have various types of diseases. As different diseases have distinct metabolomic profiles and metabolites can interact with proteins, it is legitimate to hypothesize that metabolomic profiles in plasma may have the capacity to, at least partially, drive the formation of a personalized protein corona. To test this hypothesis, we employed a multi-scale approach composed of coarse-grained (CG) and all atom (AA) molecular dynamics (MD) simulations to probe the role of glucose and cholesterol (model metabolites in diabetes and hypercholesterolemia patients) in the interaction of fibrinogen protein and polystyrene NPs. Our results revealed that glucose and cholesterol had the capacity to induce substantial changes in the binding site of fibrinogen to the surface of NPs. More specifically, the simulation results demonstrated that increasing the metabolite amount could change the profiles of fibrinogen adsorption and replacement, what is known as the Vroman effect, on the NP surface. In addition, we also found out that metabolites can substantially determine the immune triggering potency of the fibrinogen–NP complex. Our proof-of-concept outcomes further emphasize the need for the development of patient-specific NPs in a disease type-specific manner for high yielding and safe clinical applications.

Mechanosensitive (MS) channels are ubiquitous molecular force sensors that respond to a number of different mechanical stimuli including tensile, compressive and shear stress. MS channels are also proposed to be molecular curvature sensors gating in response to bending in their local environment. One of the main mechanisms to functionally study these channels is the patch clamp technique. However, the patch of membrane surveyed using this methodology is far from physiological. Here we use continuum mechanics to probe the question of how curvature, in a standard patch clamp experiment, at different length scales (global and local) affects a model MS channel. Firstly, to increase the accuracy of the Laplace’s equation in tension estimation in a patch membrane and to be able to more precisely describe the transient phenomena happening during patch clamping, we propose a modified Laplace’s equation. Most importantly, we unambiguously show that the global curvature of a patch, which is visible under the microscope during patch clamp experiments, is of negligible energetic consequence for activation of an MS channel in a model membrane. However, the local curvature (R_L < 50) and the direction of bending are able to cause considerable changes in the stress distribution through the thickness of the membrane. Not only does local bending, in the order of physiologically relevant curvatures, cause a substantial change in the pressure profile but it also significantly modifies the stress distribution in response to force application. Understanding these stress variations in regions of high local bending is essential for a complete understanding of the effects of curvature on MS channels.

A semianalytical thermoelasticity solution for thick-walled finite-length cylinders made of functionally graded (FG) materials is presented. The governing partial differential equations are reduced to ordinary differential equations using Fourier expansion series in the axial coordinate. The radial domain is divided into some virtual subdomains in which the power-law distribution is used for the thermomechanical properties of the constituent components. Imposing the necessary continuity conditions between adjacent subdomains, together with the global boundary conditions, a set of linear algebraic equations are obtained. Solution of the linear algebraic equations yields the thermoelastic responses for each subdomain as exponential functions of the radial coordinate. Some results for the stress, strain, and displacement components through the thickness and along the length are presented due to uniform internal pressure and thermal loading. Based on the results, the gradation of the constitutive components is a significant parameter in the thermomechanical responses of FG cylinders.

The aim of this work is to develop a model to continuously predict inhomogeneous and homogeneous swelling behavior of temperature-sensitive poly-(N-isopropylacrylamide) hydrogels. Employing this model, some benchmark homogeneous problems such as free, unidirectional constrained and biaxial constrained swelling as well as swelling of core-shell structures are investigated. The main advantage of the model is its ability to solve inhomogeneous deformations due to a stable behavior in the vicinity of the phase transition temperature. Therefore, inhomogeneous swelling of a spherical shell on a hard core with application to microfluidics is analytically and numerically investigated for various thicknesses of the shell. Based on the solved examples, it is shown that the model possesses continuity and stability in the vicinity of the phase transition temperature.