Nanoparticles and biological cells: From atomistic simulations to membrane diagnostics

Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. The delivery of drugs, antigens, and imaging agents benefit from using nanotechnology-based carriers. However, from the entry of the therapeutic nanoparticle into the host ́s blood circulation, the nanoparticle faces a long journey to its intended destination. During that journey, there are several barriers that need to be overcome. These hurdles are often neglected or disregarded in physiochemical evaluations of the future possibilities of nanotechnology to deliver agents to specific targets. In this talk we report on our latest results on the interactions of nanoparticles with cellular membranes. The two main questions we want to address are: 1) what are the physicochemical characteristics of nanomaterials that drive their entry into cells? And, 2) can we design nanomaterials in order to achieve selective mode of entry into cells? The results will focus on carbonaceous nanoparticles, including a new class of compounds, carbonaceous quantum dots, which have recently emerged and ignited tremendous research interest. Their favorable characteristics include size- and wavelength-dependent luminescence, resistance to photobleaching, bio-conjugation, and functionalization to produce chiral nanostructures. Carbon-based quantum dots show promise in areas such optoelectronics, catalysis, bioanalysis and drug delivery. Atomistic simulations in conjunction with precise chemical and biophysical experiments are the distinguishing characteristics of this effort. Molecular dynamics simulations will examine the effects of nanoparticles parameters, such as size and chemical composition, on the entry mode of nanoparticles into cells. A conceptual framework is presented that envisions possible routes for the design of nanomaterials for nanomedicine applications

Combustion-generated nanoparticles produced in a benzene flame: A multiscale approach

This paper details the multiscale methodology developed to analyze the formation of nanoparticles in a manner that makes it possible to follow the evolution of the structures in a chemically specific way. The atomistic model for particle inception code that combines the strengths of kinetic Monte Carlo and molecular dynamics is used to study the chemical and physical properties of nanoparticles generated in a premixed fuel-rich benzene flame, providing atomistic scale structures (bonds, bond angles, dihedral angles) as soot precursors evolve into a three-dimensional structure. Morphology, density, porosity, and other physical properties are computed. Two heights corresponding to two different times in the benzene flame, experimentally studied by Bittner and Howard [Proc. Combust. Inst. 18, 1105 (1981)], were chosen to examine the influence of different environments on structural properties of the particles formed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87870/2/054302_1.pd

Mutual diffusion coefficients of heptane isomers in nitrogen: A molecular dynamics study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98650/1/JChemPhys_134_044537.pd

Development of Comprehensive Detailed and Reduced Reaction Mechanisms for Syngas and Hydrogen Combustion

The collaborative research initiative culminated in amassing a substantial combustion database of experimental results for dry and moist mixtures of syngas and hydrogen (SGH), including autoignition times using a rapid compression machine as well as laminar flame speeds using a counterflow twin-flame configuration. These experimental data provided the basis for assessment of the kinetics of SGH combustion at elevated pressures using global uncertainty analysis methods. A review of the fundamental combustion characteristics of H{sub 2}/CO mixtures, with emphasis on ignition and flame propagation at high pressures was also conducted to understand the state of the art in SGH combustion. Investigation of the reaction kinetics of CO+HO{sub 2}{center_dot} {yields} CO{sub 2} + {center_dot}OH and HO{sub 2}+OH {yields} H{sub 2}O+O{sub 2} by ab initio calculations and master equation modeling was further carried out in order to look into the discrepancies between the experimental data and the results predicted by the mechanisms

Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and cardiovascular events in atrial fibrillation. a prospective multicenter cohort study

Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events (CVEs) independently from metabolic syndrome (MetS) is still matter of debate. Aim of the study was to investigate the risk of CVEs in a high-risk population of patients with non-valvular atrial fibrillation (AF) according to the presence of MetS and NAFLD. Prospective observational multicenter study including 1,735 patients with non-valvular AF treated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). NAFLD was defined by a fatty liver index≥60. We categorized patients in 4 groups: 0=neither MetS or NAFLD (38.6%), 1=NAFLD alone (12.4%), 2=MetS alone (19.3%), 3=both MetS and NAFLD (29.7%). Primary endpoint was a composite of CVEs. Mean age was 75.4±9.4years, and 41.4% of patients were women. During a mean follow-up of 34.1±22.8months (4,926.8 patient-years), 155 CVEs were recorded (incidence rate of 3.1%/year): 55 occurred in Group 0 (2.92%/year), 12 in Group 1 (2.17%/year), 45 in Group 2 (4.58%/year) and 43 in Group 3 (2.85%/year). Multivariable Cox regression analysis showed that use of DOACs, and female sex were inversely associated with CVEs, whilst age, heart failure, previous cardiac and cerebrovascular events, and group 2 (Group 2, Hazard Ratio 1.517, 95% Confidence Interval, 1.010-2.280) were directly associated with CVEs. In patients with AF, MetS increases the risk of CVEs. Patients with NAFLD alone have lower cardiovascular risk but may experience higher liver-related complications