Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session A13: Brain Organoids: From morphogenesis to metamaterialsInvited
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Sponsoring Units: DBIO Chair: Manu Prakash, Stanford University Room: Room 238 |
Monday, March 6, 2023 8:00AM - 8:36AM |
A13.00001: Linear viscoelastic properties of the vertex model for biological tissues Invited Speaker: Andrej Kosmrlj Biological tissues can repair themselves, respond to environmental changes and grow without compromising their integrity. Consequently, they exhibit complex viscoelastic rheological behavior where constituent cells actively tune their mechanical properties to change the overall response of the tissue, e.g., from solid-like to fluid-like. Mesoscopic mechanical properties of tissues are commonly modeled with the vertex model. While previous studies have predominantly focused on the rheological properties of the vertex model at long time scales, we systematically studied the full dynamic range by applying small oscillatory shear and bulk deformations in both solid-like and fluid-like phases. Furthermore, we considered systems with external (e.g., cell-substrate) and internal (e.g., cell-cell) dissipation mechanisms. We showed that the linear rheological response of the system can be described using the normal mode formalism, where each normal mode responds with a characteristic relaxation timescale. This semi-analytical method based on normal modes allows full characterization of the potentially complex linear rheological response of the system at all driving frequencies and identification of collective excitations. We show that internal and external dissipation mechanisms lead to qualitatively different rheological behaviors, which is particularly pronounced at high driving frequencies. Our findings, therefore, underscore the importance of microscopic dissipation mechanisms in understanding the rich rheological behavior of biological tissues. |
Monday, March 6, 2023 8:36AM - 9:12AM |
A13.00002: Brain organoids: New models to study neural development and disease Invited Speaker: Momoko Watanabe The human brain, particularly the forebrain, has many features and functions that are distinct to humans. To effectively understand human disease mechanisms and identify novel therapies, it is critical to have access to a human tissue-based model for experimental study. Many clinical trials of neurological disorders have been unsuccessful perhaps because they have been designed based on animal models and have not taken into account some cross-species differences. Human fetal tissue is unquestionably valuable as it is the gold standard to which results need to be compared. However, there are many ethical and practical concerns, including the limited availability of human brain samples particularly at early fetal stages, making it very difficult to conduct controlled, mechanistic experiments and screen for drugs. These considerations illustrate the need for alternative tools to create human brain cells, and ideally tissues with functional neural networks. Consequently, a great deal of attention has been placed on the generation of in vitro models using human pluripotent stem cells (hPSCs) to recapitulate aspects of human development and disease. Recently, several protocols for brain organoids (aka “mini-brain in a dish”), in which hPSCs are induced to form three-dimensional tissue structure that recapitulates the developing brain, have been established. While progress in organoid technology is rapidly advancing, many challenges remain, including rampant batch-to-batch and line-to-line variability, unwanted differentiation into different classes of neural cells and other tissue types, and the paucity of direct comparisons to native human tissue. We established reproducible and efficient methods for cortical organoid differentiation that faithfully recapitulate in vivo neocortical development transcriptionally, structurally, and functionally. We also applied the organoid system to model neurodevelopmental diseases including Congenital Zika Syndrome and Rett Syndrome. Taken together, our study showed a cortical organoid system could recapitulate early human development and be an ideal platform to model disease, providing an unprecedented opportunity to study brain structures with multidisciplinary approaches. |
Monday, March 6, 2023 9:12AM - 9:48AM |
A13.00003: Brain Folds and the Extracellular Matrix: Lessons from Brain Organoids Invited Speaker: Orly Reiner Neurodevelopmental brain disorders include a spectrum of diseases, ranging from brain malformations, such as microcephaly (small brain) and lissencephaly (smooth brain), through different forms of epilepsy, to intellectual disability, autism spectrum disorders, and schizophrenia. Our studies focused on haploinsufficient mutations in LIS1 that result in lissencephaly. Using different brain organoid models, we detected changes in the matrisome, which includes components of the extracellular matrix (ECM) and their modulating enzymes. We identified the molecular mechanisms involved in changing gene expression and demonstrated how the physical properties of the organoids change. We believe that our studies are important for understanding how the brain folds during embryonic development and what goes wrong in case of diseases. |
Monday, March 6, 2023 9:48AM - 10:24AM |
A13.00004: Functional neuronal circuitry and oscillatory dynamics in human brain organoids Invited Speaker: Kenneth Kosik Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks. |
Monday, March 6, 2023 10:24AM - 11:00AM |
A13.00005: Towards building brains using in vitro biology across scales Invited Speaker: J. M Schwarz How does the brain work? One could argue that to understand how something works, one must be able to build it. Indeed, Nature has figured out the blueprint for building a brain, if you will, in a process known as evolution. So now one asks: How does such a brain blueprint emerge? Since this question is rather tricky to answer quantitatively, is there a brain-like in vitro setting to study the emergence of a blueprint outside of a developing embryo where one can genetically, chemically, and mechanically perturb the process as it occurs? Indeed, there is. The setting is known as brain organoids. Brain organoids begin as a clump of cells and eventually develop into a network of firing neurons. I will discuss work on building minimal, multiscale computational models to predict the structure of a brain organoids early on in development with an eye towards designing new brain organoid structures, or architectures, that are optimized to solve a particular class of computational problems. |
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