The Binding and Aggregation of Anisotropic Nanoparticles on Cylindrical Lipid Membranes

Golgi and endoplasmic reticulum in eukaryotic cells, owe their complex membrane conformations to specialized curvature inducing proteins. Using coarse-grained molecular dynamics simulations, we investigated the aggregation and binding of anisotropically curved nanoparticles to cylindrical lipid membranes. Here we consider only the case where the nanoparticle– nanoparticle interaction is repulsive and only the concave surface of the nanoparticle interacts attractively with the lipid head groups. The ability of a nanoparticle to bind to a cylindrical membrane depends on the nanoparticlelipid interaction strength, mismatch in nanoparticle-membrane curvature, and the nanoparticles's arclength. We found that the minimum interaction strength required for a single nanoparticle binding increases with mismatch in nanoparticle-membrane curvature or increasing the nanoparticle arclength. Additionally, nanoparticles were found to accommodate a tilt angle on cylindrical membranes having a radius of curvature less that of the bound nanoparticles. This tilt angle is well maintained for nanoparticles with large arclengths, while shorter nanoparticles are able to rotationally diffuse more freely. These results are consistent for larger numbers of nanoparticles where they aggregate into various structures depending on nanoparticle-lipid interaction strength, mismatch in nanoparticle-membrane curvature, and the nanoparticles's arclength. This aggregation by many nanoparticle is reminiscent of protein aggregates formed by the BAR-protein family, in spite of the lack of nanoparticle-nanoparticle interactions. Presenter Name: Amy Koury Affiliation: Wright Medical Technology, Memphis, TN CoAuthors: Nate Webb, Jesse Fleming, Doug Linton, Jon Moseley Title: Wear of a Stabilized Crosslinked UHMWPE Total Ankle Replacement Abstract: Abstract withheld per request by company for confidentiality. Presenter Name: Andrew S Curry Classification: Graduate Affiliation: Biomedical Engineering, University of Alabama, Birmingham Advisor and/or CoAuthors: Nicholas W Pensa, Jennifer L. Bain, Michael S. Reddy, Susan L. Bellis Title: BMP2-Derived Peptides with Polyglutamate Domains Anchor onto Bone Graft Materials Abstract: The osteoinductive factor, BMP2, has been passively adsorbed to commercial bone graft materials to improve osseointegration, however BMP2 disseminates quickly from the graft, resulting in inflammation. Previously we identified a molecular domain of 7 glutamates (E7) which tightly binds to hydroxyapatite, a common graft material. We hypothesize a bioactive peptide derived from BMP2 with an attached E7 domain (E7BMP2pep) can anchor to hydroxyapatite, increasing bone regeneration without evoking a deleterious immune response. Osteoblastic cells were treated with BMP2pep, with or without E7, to measure osteogenic cell signaling. Peptide-coated hydroxyapatite particles were implanted in rat cranial defects and evaluated by H&E and immunohistochemistry to analyze bone formation, presence of T cells (CD3), and vascularization (CD34). In vitro assays showed that the E7 domain greatly improves peptide anchoring to hydroxyapatite without diminishing BMP2pep’s capacity to stimulate BMP2-dependent signaling (pSMAD activation) and osteoblastic differentiation (upregulation of alkaline phosphatase, ALP). In fact, cells treated with E7-BMP2pep had equivalent levels of induced ALP expression compared with full-length rBMP2. In vivo studies of implanted E7-BMP2pep-coated hydroxyapatite revealed that the peptide strongly stimulated bone formation, and did not hinder vascularization. Furthermore, there was minimal T cell infiltration associated with the E7-BMP2pep group compared with rBMP2-coated samples. E7-BMP2pep offers a valid alternative to full-length rBMP2 because it can prolong osteoblastic signaling at the graft site by strongly adhering to hydroxyapatite, resulting in equivalent bone formation compared to rBMP2, without the inflammatory response commonly seen with rBMP2 treatment. Acknowledgement: NIH R01 DE024670; DART T90DE022736 Presenter Name: Andrew Dunn Classification: Graduate Student Affiliation: Department of Biomedical Engineering, Parks College of Engineering, Aviation, and Technology, Saint Louis University Department of Orthopedic Surgery, Saint Louis University Advisor and/or CoAuthors: Gabriel Haas, Madison Marcinczyk, Muhamed Talovic, Robert Scheidt, Anjali Patel, Mark Schwartz, Katherine R Hixon, Hady Elmashhady, Sarah H McBride-Gagyi, Scott A Sell , Koyal Garg Title: Biomimetic Collagen Laminin-111 Sponges Promote Myogenic Regeneration in a Murine Volumetric Muscle Loss-Wounding Model Abstract: Musculoskeletal injuries are among the most common disabling injuries sustained by athletes and soldiers. Most of these injuries involve volumetric muscle loss (VML), defined as the as the surgical or traumatic loss of muscle tissue with resultant functional impairment. While skeletal muscle is remarkably regenerative, VML injuries are irrecoverable due to the complete loss of the basal lamina and resident satellite cells. There are no approved therapies for the treatment of muscle tissue following trauma, presenting an opportunity to develop tissue-engineered scaffolds for muscle tissue regeneration. To improve regeneration of skeletal muscle, we have developed biomimetic sponges composed of collagen, gelatin, and laminin (LM)-111. Collagen and LM-111 are crucial components of the muscle extracellular matrix and were chosen to impart bioactivity whereas gelatin was used to provide mechanical strength to the scaffold. Morphological and mechanical evaluation of the sponges showed porous structure, water-retention capacity and a compressive modulus of 590kPa. In vitro testing revealed that compared to pure gelatin sponges, the biomimetic sponges supported greater C2C12 myoblast infiltration, myokine production and myogenic marker expression. The biomimetic sponges were implanted in a mouse model of VML. At 2 weeks post-injury, sponge treated VML injured muscles showed constructive remodeling at the site of injury with the elevated presence of satellite, endothelial and inflammatory cells compared to untreated VML injured muscles. The sponge treated muscles showed several small diameter myosin myofibers in the defect region. In support, the protein expression of MyoD and desmin was significantly higher, while that of myogenin trended higher on the sponge treated injured muscles. However, the expression of heat shock protein (HSP)-70, a marker of cellular stress was lower with sponge treatment. These results suggest that implantation of the biomimetic sponges is able to promote myogenic activity in the VML injured muscles. Presenter Name: Brandico Barr Classification: Undergraduate Affiliation: Biomedical Engineering, University of Memphis, Herff College of Engineering, Memphis, TN Advisor and/or CoAuthors: Jessica Amber Jennings, PhD, Joel Bumgardner PhD Title: Chitosan Composite Coating for Bone Growth in Musculoskeletal Implants Abstract: Over 4 million people in the United States alone have at least one internal fixation implant, and due to the rise of elderly need for implants, that number is only increasing. With dental and musculoskeletal implants, integration of implant into bone is a critical step. Release of bioactive molecules from implant coatings may improve bone growth. Recent studies have shown that members of the statin drug family, such as simvastatin, have similar osteogenic properties to growth factors like bone morphogenetic protein-2. However, the hydrophobic nature of statins presents difficulties for loading into traditional local delivery biomaterials. In this study, we evaluated a chitosan composite coating with calcium-phosphate nanospheres loaded with simvastatin (CaP-SMV) to release osteogenic factors from implants. The main goal of this experiment was to determine the physiochemical properties of the coating by performing a 7 day elution study. Coatings were made with 2% chitosan solution, 1mg/mL simvastatin with a 1:3 ratio of calcium phosphate. High performance liquid chromatography (HPLC) was used to detect simvastatin. Results indicated that the CaP-SMV coating eluted less simvastatin than the pure simvastatin coating. Future studies include spectroscopy to visualize the physical properties of the coating. Presenter Name: Caleb Gallops Classification: Graduate Student Affiliation: Chemistry, University of Memphis, College of Arts & Sciences, Memphis, TN Advisor and/or CoAuthors: Dr. Yongmei Wang, Dr. Jesse Ziebarth, Chang Yu Title: Effects of Protonation and Salt Concentration on the Structure of a Polylethylenimine (PEI) in Water Abstract: Polyethylenimine (PEI) is the subject of intense study within the field of non-viral gene delivery due to its promising potential as a transfection vector. The polycationic PEI chains bind to the anionic phosphate backbone of nucleic acids, forming complexes and facilitating the delivery of genetic materials. The success of PEI as non-viral gene delivery vector is linked with its pH-responsive properties as PEI becomes more protonated when the pH is lowered. This is thought to cause PEI/nucleic acid complexes to escape from the lysosome as the endosomal pH decreases, resulting in high transfection efficiencies. Computational studies can provide insight on the structural and dynamical changes of PEI chains at different protonation states and different salt concentrations. The goal of this study was to determine the effect of salt concentration on the structure and dynamics of PEI at various protonation states. Series of molecular dynamics simulations were performed on a linear PEI chain in a periodic box of explicit water and NaCl ions at 0mM, 150mM and 500mM. Within each series, nine simulations were performed with protonation states ranging from zero protonation to full protonation. The radius of gyration, persistence length, average N-N distance and average Cl coord