Biophysics Seminar day - 04/16/2018 - 11:30am-1:50pm - 1080 Physics Research Building

11:30-12:30 Flex your mussels! Making Soft, Strong and Tough Materials Inspired by Nature
Megan Valentine, University of California at Santa Barbara

Marine mussels create an array of adhesive contacts (the byssus) to secure themselves to rocks, wood, metals and other mussels in the harsh conditions of the intertidal zone. Their superb mechanical and adhesive performance has served as inspiration to create mussel-inspired materials for a wide range of applications ranging from surgical glues to primers and coatings. Historically, much of this success has relied on mimicry of the molecular properties of the mussel's adhesive interfacial proteins. By contrast, the translation of the meso- to macro-scopic properties of the natural materials has been comparatively unexplored, providing rich opportunities for further property enhancement to create tough, durable, load-bearing materials. Here, I will present my laboratory's recent work characterizing the role of geometry and mechanics in mussel byssal plaques. Experimentally, we observe the dynamics of mussel plaques as they debond from glass using a custom built load frame with integrated dual view imaging capabilities, under monotonic and cyclic loading. We pair these mechanical tests with ultrastructural analysis to understand the molecular origins of strength and toughness. Using insights from the natural materials, we then create high-performance synthetic materials that are extremely strong without compromising extensibility, as well as mussel-inspired 3D structures with tunable stiffness and strength. These innovations open new possibilities for applications of mussel-inspired materials in packaging, soft robotics, and connective tissue repair, and demonstrate the importance of understanding the multiscale, multiphase properties of biological materials.

12:50-1:20 DNA Nanocalipers to Probe Structure and Dynamics of Chromatin
Jenny Le, Castro lab

Nucleosomes, consisting of genomic DNA wrapped around a protein core, assemble into higher orders of chromatin structure to compact DNA. Tools to probe site-specific chromatin at the 10-100nm lengthscale (relevant for gene regulation) and to apply tensile or compressive forces at targeted sites could greatly improve insight into how chromatin structural dynamics regulate DNA processing. We designed, constructed, and implemented a nanocaliper via DNA origami, a method using DNA as building blocks to assemble complex 3D nanostructures. Our nanocalipers are hinge-like joints that consist of two 70nm rigid arms, each made up of bundled DNA helices, connected by single stranded DNA.

For proof-of-concept, we bind the two nucleosomal DNA ends to the ends of nanocaliper arms. Here, the caliper angle reports the nucleosome end-to-end distance. We demonstrated the nanocaliper can detect nucleosome conformational changes via transcription activator Gal4-VP16 binding. The caliper also significantly increases the probability of Gal4-VP16 occupancy by applying a tension to partially unwraps the nucleosome. This suggests that our DNA nanocalipers can report biologically relevant conformational changes and manipulate nucleosomes to test their function.

We developed a model that accurately describes our nucleosome-nanocaliper assemblies as concomitantly (simultaneous but independent) unwrapping, further validated by hexasome-nanocaliper measurements. This model demonstrates nucleosome unwrapping is sensitive to the caliper's applied force, motivating a design that applies tunable tensile/compressive forces. We created a new nanocaliper with tunable stiffness and equilibrium angle, for example, to incorporate a sample and then apply a tensile/compressive force.

This project provides a foundation of future mesoscale studies of nucleosome arrays and chromatin structural dynamics. These tools could directly monitor or manipulate local chromatin structure and dynamics in single living cells

1:20-1:50 Effects of Ionizing Irradiation on Mouse Diaphragmatic Skeletal Muscle.
Tingyang Zhou, Luo lab

Undesirable exposure of diaphragm to radiation during thoracic radiation therapy has not been fully considered over the past decades. Our study aims to examine the potential biological effects on diaphragm induced by radiation. One-time ionizing irradiation of 10 Gy was applied either to the diaphragmatic region of mice or to the cultured C2C12 myocytes. Each sample was then assayed for muscle function, oxidative stress, or cell viability on days 1, 3, 5, and 7 after irradiation. Our mouse model shows that radiation significantly reduced muscle function on the 5th and 7th days and increased reactive oxygen species (ROS) formation in the diaphragm tissue from days 3 to 7. Similarly, the myocytes exhibited markedly decreased viability and elevated oxidative stress from days 5 to 7 after radiation. These data together suggested that a single dose of 10-Gy radiation is sufficient to cause acute adverse effects on diaphragmatic muscle function, redox balance, and myocyte survival. Furthermore, using the collected data, we developed a physical model to formularize the correlation between diaphragmatic ROS release and time after irradiation, which can be used to predict the biological effects of radiation with a specific dosage. Our findings highlight the importance of developing protective strategies to attenuate oxidative stress and prevent diaphragm injury during radiotherapy.

Last update: 4/11/2018, Ralf Bundschuh