We study, by means of mean-field calculations and Monte Carlo simulations of a lattice gas model, the distribution of adhesion sites of a bilayer membrane and a supporting flat surface. Our model accounts for the many-body character of the attractive interactions between adhesion points induced by the membrane thermal fluctuations. We show that while the fluctuation-mediated interactions alone are not sufficient to allow the formation of aggregation domains, they greatly reduce the strength of the direct interactions required to facilitate cluster formation. Specifically, for adhesion molecules interacting via a short-range attractive potential, the strength of the direct interactions required for aggregation is reduced by about a factor of two to below the thermal energy k(B)T.
Adhesion bonds between membranes and surfaces are attracted to each other via effective interactions whose origin the entropy loss due to the reduction in the amplitude of the membrane thermal fluctuations in the vicinity of the adhesion bonds. These fluctuation-induced interactions are also expected to drive the adhesion bonds toward the rim of the cell, as well as toward the surfaces of membrane inclusions. In this paper, we analyze the attraction of adhesion bonds to the cell inner and outer boundaries. Our analysis shows that the probability distribution function of a single (diffusing) adhesion bond decay algebraically with the distance from the boundaries. Upon increasing the concentration of the adhesion bonds, the attraction to the boundaries becomes strongly self-screened.
The advent of recombinant DNA technology fundamentally altered the drug discovery landscape, replacing traditional small-molecule drugs with protein and peptide-based biologics. Being susceptible to degradation via the oral route, biologics require comparatively invasive injections, most commonly by intravenous infusion (IV). Significant academic and industrial efforts are underway to replace IV transport with subcutaneous delivery by wearable infusion devices. To further complement the ease-of-use and safety of disposable infusion devices, surface disinfection of the drug container can be automated. For ease of use, the desired injector is a combination device, where the drug is inside the injector as a single solution combination device. The main obstacle of the desired solution is the inability to sterilize both injector and drug in the same chamber or using the same method (Gamma for the drug and ETO for the injector). This leads to the assembly of both drug container and injector after sterilization, resulting in at least one transition area that is not sterilized. To automate the delivery of the drug to the patient, a disinfection step before the drug delivery through the injector is required on the none-sterilized interface. As an innovative solution, the autoinjector presented here is designed with a single ultraviolet light-emitting diode (UV LED) for surface disinfection of the drug container and injector interface. In order to validate microbial disinfection similar to ethanol swabbing on the injector, a bacterial 3 or 6 log reduction needed to be demonstrated. However, the small disinfection chamber surfaces within the device are incapable of holding an initial bacterial load for demonstrating the 3 or 6 log reduction, complicating the validation method, and presenting a dilemma as to how to achieve the log reduction while producing real chamber conditions. The suggested solution in this paper is to establish a correlation model between the UV irradiance distribution within the disinfection chamber and a larger external test setup, which can hold the required bacterial load and represents a worse-case test scenario. Bacterial log reduction was subsequently performed on nine different microorganisms of low to high UV-tolerance. The procedure defined herein can be adopted for other surface or chamber disinfection studies in which the inoculation space is limited.
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