Bulletin of the American Physical Society
2024 APS March Meeting
Monday–Friday, March 4–8, 2024; Minneapolis & Virtual
Session T55: Biomaterials and NanotechnologyFocus Session
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Sponsoring Units: DBIO DSOFT Chair: Ramakrishna Podila, Clemson University Room: 204AB |
Thursday, March 7, 2024 11:30AM - 12:06PM |
T55.00001: Spectroscopic insights into the nano-bio interface Invited Speaker: Ramakrishna Podila The similar size scale of biomolecules and nanomaterials implies a strong interaction between these entities, which facilitates novel biophysics at the nanoscale. The advancement and acceptance of personalized nanomedicine relies heavily on a holistic interdisciplinary understanding and alleviation of the undesired impacts of emerging nanomaterials on physiological and environmental systems. For instance, the interaction between nanomaterials and biomolecules elicits strongly adverse allergic and immune response, which must be mitigated for treating disease through nanomedicine. As my talk will elucidate, spectroscopy is an important tool for understanding nano-bio interfaces. Optical spectroscopic tools can provide deep insights into nanomaterial interaction with proteins, cells, and organelles, leading to the formation of protein coronas, changes in intracellular uptake, altered physiological response and other biophysical processes. In this talk, I will provide an overview of the nano-bio interface from the standpoint of nanotoxicity. I will discuss our collaborative work on defected nanomaterials, protein corona formation, and delve into some unexplored quantum effects at the nano-bio interface. |
Thursday, March 7, 2024 12:06PM - 12:18PM |
T55.00002: Real-Time Detection and Analysis of Biomolecular Interactions in Crowded environment using Nanopipette Santosh Khatri, Jin He Biomolecular interactions play a crucial role in various cellular communication and physiological pathways. Understanding these interactions in the native environment is essential for the development of novel therapeutic strategies for numerous diseases. However, the study of biomolecular interactions is challenging and lacks appropriate tools. In this talk, I will introduce a low-cost, and label-free based detection technique, for real-time detection and analysis of biomolecular interactions in a crowded environment. This innovative approach involves the jamming of biomolecules with the strategic combination of hard confinement via a long taper funnel-shaped tip of a quartz nanopipette tip at the cis side and soft confinement facilitated by hydrogel at the trans side. Notably, the degree of biomolecular crowding can be monitored based on the direction of the ionic current signal. Moreover, upon the co-localization of the ligand with the receptor within the nanoconfinement, the complexes formed at the single molecule level can be detected individually at the nanopore outlet as an ionic current signal. By modulating the level of crowding, the interaction between biomolecules and the percentages of complex formation can also be modulated. The coupling strength between biomolecules is reflected in time-dependent ionic current recordings. This detection strategy has several advantages over traditional ensemble methods and can sensitively detect interactions in small molecules (≤1 kDa) in a crowded environment. Therefore, this methodology holds the promise to revolutionize the study of biomolecular interactions in real-time and utilize them to screen for new drug candidates. |
Thursday, March 7, 2024 12:18PM - 12:30PM |
T55.00003: Control of biomechanical properties by cell encapsulation Udathari Kumarasinghe, Cristian Staii, David Kaplan, Ying Chen Encapsulation of single cells is a powerful technique which has been used in various fields such as biotechnology, regenerative medicine, and drug delivery. Single cell encapsulation can be used to protect immune cells by providing cytocompatible coatings to strengthen cells against mechanical and environmental stresses. Silk fibroin, derived from the silkworm Bombyx mori is a promising biomaterial for encapsulation due to its biocompatibility and capacity to maintain cell functionality. In this work, THP-1 cells, a human leukemia monocytic cell line, were encapsulated with chemically modified charged silks, ionomers, through electrostatic layer-by-layer deposition. We will present findings on cell viability and functionality, as well as the cytocompatibility of the silk material in these systems. We measured elasticity maps and cellular stiffness using the atomic force microscope (AFM). Additionally, by applying consistent sheer stress to cells both pre and post-encapsulation, we observed that both stiffness and cytoprotection of the cells increased after the silk encapsulation. Such encapsulation offers unique opportunities to fine-tune the cellular assembly and biomechanics, while also promoting compatible systems that protect cells both during the biomaterial deposition process as well as in the subsequent applications of these coated cells. This work provides significant insights into the design of novel biomaterial interfaces for cellular protection and functionalization. |
Thursday, March 7, 2024 12:30PM - 12:42PM |
T55.00004: Biophysical parameters of bacteriophage adsorption to host cells Jyot Antani, Timothy Ward, Isabella R Graf, Thierry Emonet, Paul Turner Bacteriophages (phages), viruses that infect bacteria, represent the most abundant biological entities on Earth. Phages initiate a new infection cycle by binding to specific proteins, polysaccharides, or appendages on host bacterial surfaces- termed phage receptors. While the phage receptors, different for each phage species, are routinely characterized through genetic assays, the dynamics of phage attachment (adsorption) are poorly understood. The classical understanding of phage adsorption is derived from flasks- and plate-based assays, which provide ensemble estimates of the adsorption rate. Characterization of stochastic dynamics of phage-host interactions requires single cell and single phage measurements. |
Thursday, March 7, 2024 12:42PM - 12:54PM |
T55.00005: Solubilization of Hydrophobic Astaxanthin in Water by Physical Association with Phytoglycogen Nanoparticles Nicholas van Heijst, John R Dutcher Phytoglycogen (PG) is a soft glucose-based dendrimer produced as compact nanoparticles in the kernels of sweet corn. Its softness and deformability, combined with its biocompatibility, non-toxicity and digestibility, make it an attractive choice for biomedical applications such as bioactive delivery. This is a challenge since most bioactives are hydrophobic. In the present study, we demonstrate that PG can be used as an effective solubilizing agent for the hydrophobic carotenoid astaxanthin (AXT), which has reported health benefits. We have developed a procedure that results in a strong physical association of AXT to PG without using chemicals such as surfactants. By combining AXT dissolved in acetone with PG dispersed in water, evaporating the acetone, and removing the water, we obtain a dry powder of AXT-PG that can be easily redispersed in water, increasing the effective solubility of AXT in water by more than a factor of 1012 relative to that calculated for AXT in water. Aqueous dispersions of AXT-PG are stable for several months, as measured using UV-Vis spectroscopy. UV-Vis measurements also allowed us to quantify the aggregation state of AXT on the surface of the PG particles. Our results demonstrate the promise of using PG as an effective solubilizing and stabilizing agent for hydrophobic compounds in water. |
Thursday, March 7, 2024 12:54PM - 1:06PM |
T55.00006: Single particle tracking to probe small molecule ligand-receptor interactions Jessica Chiu Ligand-receptor interactions are a key bionanoscale recognition event in endocytosis, endosomal trafficking, and immune system responses. Small molecule ligand-receptor interactions are not well-studied and could elucidate why nanoparticles with small molecule targeting ligands are successful in vitro but not clinically. In this presentation, the effect of nanoparticle design on promoting successful targeting events was measured by analyzing the dynamics of small molecule ligand-receptor interactions. With folic acid-folate receptor alpha (FA-FOLR1) as a case study, single particle trajectories of FA-conjugated nanoparticles were tracked on SKOV-3 cancer cell membranes in vitro using differential interference contrast (DIC) microscopy. The trajectories were quantitatively categorized with mean square displacement analysis into diffusion modes. The distribution of diffusion modes can be correlated to the biological nature of FA-FOLR1 interactions. These results suggest that anisotropic nanoparticle shape and a short linker molecule connecting folic acid to the nanoparticle surface are key design considerations for nanoparticles with small molecule targeting ligands. |
Thursday, March 7, 2024 1:06PM - 1:18PM |
T55.00007: Immune stealth VP28-conjugated heparin nanocomplex development for reducing self-aggregation risk of heparin Chia-Ching Chang, Hussein R Hussein, Chia-Yu Chang, Chih-Yu Yang, Yu-Chaun Liang, Lik Voon Kiew Unfractionated heparins (heparin) are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, self-aggregation induced life-threatening complications. We proposed that the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. Therefore, an immunostealth recombinant viral capsid protein (VP28) was conjugated with heparin to form a novel nanocomplex (VP28-heparin). The size of VP28-heparin nanocomplexes is approximately 9 nm and this small particle does not induce immune responses in animal model systems. Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dose in vivo. Thus, an effective and safe heparin derivative, VP28-heparin, has been developed as proposed and may be used for biomedical applications. |
Thursday, March 7, 2024 1:18PM - 1:30PM |
T55.00008: Age and temperature effects on collagen structure, stability and mechanics Nancy R Forde, Daniel Sloseris, Alaa Al-Shaer Collagen is the predominant structural protein in humans, representing over 25% of protein mass in our bodies, and fulfilling key mechanical and signalling functions in the extracellular matrix and connective tissues. As we age, collagens gradually acquire nonenzymatic chemical modifications known as Age-related Glycation End-products (AGEs). How these chemical modifications affect the interplay between structure, stability and mechanics of individual collagen proteins is not known. In this study, we combine biochemical approaches with atomic force microscopy (AFM) imaging, to investigate how these properties of collagen are affected by AGEs. We furthermore study how collagen’s thermally induced denaturation at body temperatures can be understood by use of this single-molecule imaging approach. Our results provide insight into how its surrounding environment can influence the function of this important protein. |
Thursday, March 7, 2024 1:30PM - 1:42PM |
T55.00009: Rheological tunability of fibers networks with embedded magnetic particles Anupama Gannavarapu, Lucas H Cunha, Frederick C MacKintosh Magnetic nano-particles have gained popularity for in vivo applications due to their rapid, reversible, and non-invasive nature, with potential application in surgical procedures for tuning tissue stiffness and remotely controlling drug delivery. However, the effects of magnetic particles on the mechanics of collagenous tissues has not been thoroughly explored. Experimental difficulties arise from stress response measurement precision, contrasting agents' noise, the spatial dispersion of magnetic particles and dynamic measurement of rheological quantities. To address this, we present a minimalistic numerical model to study the effects of external magnetic fields on the mechanical response of nonlinear fiber networks with embedded magnetic particles. In our model, we assume that the particles are superparamagnetic and embedded into sub-isostatic fiber networks that represent collagenous tissues. Our preliminary findings suggest that the network undergoes a phase transition-like state under applied magnetic fields at zero shear. We also observe an increase in shear modulus and earlier phase transitions as we increase the magnetic particles concentration. Speculating that these observations are caused by the coupling of non-affine rearrangement and the magnetic interactions between the particles, our model is expected to provide valuable insights into the underlying mechanisms involved in tuning the mechanical properties of tissues with magnetic particles. |
Thursday, March 7, 2024 1:42PM - 1:54PM |
T55.00010: Design of Double Network Gels Using Molecular Dynamics Simulations Mauro L Mugnai, Emanuela Del Gado Multi-component gels are common in biology and display striking material properties. Indeed, the extra-cellular matrix features a combination of various proteins and sugars, including collagen, elastin, and glycosaminoglycans, and engineered double network (DN) hydrogels exhibit remarkable toughness. Understanding and controlling the properties of these networks at a molecular level requires knowledge of the way in which inter-species and intra-species interactions affect morphology and rheology of the combined gel. In order to predict properties of DNs, we designed a series of rheological tests performed on in-silico self-assembled colloidal gels. The computational model includes two-body interactions, which drive self-assembly, and three-body terms that create filamentous networks. We systematically changed the strength of inter-species two-body and three-body interactions and explored the remarkable variety of topologies and mechanical responses generated by parameter exploration. Our results underscore the richness of DN gels, illustrate how to control their properties, and set the stage for comparison with experiments. |
Thursday, March 7, 2024 1:54PM - 2:06PM |
T55.00011: Viscoelastic materials are most energy efficient when loaded and unloaded at equal rates Lucien Tsai, Paco Navarro, Elizabeth Mendoza, Emanuel Azizi, Mark Ilton Biological springs can be used in nature for energy conservation and ultra-fast motion. The loading and unloading rates of elastic materials can play an important role in determining how the properties of these springs affect movements. We investigate the mechanical energy efficiency of biological springs (American bullfrog plantaris tendon) and synthetic elastomers under symmetric rates (equal loading and unloading durations) and asymmetric rates (unequal loading and unloading durations) using novel dynamic mechanical analysis measurements. We find that mechanical efficiency is highest at symmetric rates and significantly decreases with a larger degree of asymmetry. A generalized Maxwell model with no fitting parameters captures the experimental results based on the independently-characterized linear viscoelastic properties of the materials. The model further shows that a broader viscoelastic relaxation spectrum enhances the effect of rate-asymmetry on efficiency. Overall, our study provides valuable insights into the interplay between material properties and unloading dynamics in both biological and synthetic elastic systems. |
Thursday, March 7, 2024 2:06PM - 2:18PM |
T55.00012: Growth dynamics of yeast in 3D granular media Ashitha B Arun, M Sreepadmanabh, Sunil Laxman, Tapomoy Bhattacharjee The biochemical and genetic regulation of budding yeast (Saccharomyces cerevisiae) growth dynamics has been extensively studied using homogeneous liquid and 2D culture models. The natural habitats and commercial applications of yeast, by contrast, involve complex and disordered 3D environments that are often granular in nature. These present dramatically different mechanical regimes from what can be realized using conventional culture methods. Our present study focuses on bridging this gap by investigating yeast growth dynamics in 3D porous, granular environments. We synthesize self-healing 3D viscoelastic microgels with tuneable rheological properties to investigate how stiffness and physical confinement alter the kinetics of cellular growth and proliferation. We achieve this using a combination of absorbance-based growth assays and live-cell confocal imaging. Our results will describe how the perception and subsequent response to mechanical cues regulates growth dynamics under 3D confinement in granular environments. |
Thursday, March 7, 2024 2:18PM - 2:30PM |
T55.00013: Transition metal doped ZnO ferromagnetic nanoparticles for cancer cure Aurangzeb Khan This study presents the synthesis, characterization, and potential applications of these nanoparticles in the context of cancer cure. The synthesis of transition metal-doped ZnO nanoparticles involved the incorporation of transition metals, such as cobalt (Co), iron (Fe), and manganese (Mn), into the ZnO lattice. This process was meticulously controlled to ensure the uniform dispersion of dopants within the ZnO structure. The resulting nanoparticles were characterized using a variety of techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). These analyses confirmed the successful integration of transition metals and the generation of ferromagnetic properties within the nanoparticles. The emergence of ferromagnetism in these nanoparticles at room temperature holds significant potential for cancer cure applications. One of the key avenues explored is the use of hyperthermia, where the nanoparticles can be selectively targeted to cancer cells and exposed to an external magnetic field. This localized application of heat can induce apoptosis (cell death) in cancer cells while sparing healthy tissue, making it a highly targeted and less invasive treatment option. Moreover, the nanoparticles' magnetic properties open avenues for drug delivery systems. By functionalizing the surface of these nanoparticles, anticancer drugs can be loaded and precisely delivered to tumor sites, enhancing drug efficacy while minimizing systemic side effects. The utilization of transition metal-doped ZnO ferromagnetic nanoparticles in cancer cure strategies represents a significant advancement in the field of oncology. Their unique combination of ferromagnetic behavior, biocompatibility, and tunable properties positions them as a versatile tool for both hyperthermia-based therapies and targeted drug delivery. This research bridges the gap between materials science and medical applications, offering new possibilities for more effective and less invasive cancer treatments. As cancer remains a global health challenge, these nanoparticles hold great promise in contributing to improved patient outcomes and enhanced quality of life. |
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