Biophysical Forces Research Articles

Oscillatory contractile forces refine endothelial cell-cell interactions for continuous lumen formation governed by Heg1/Ccm1.

The formation and organization of complex blood vessel networks rely on various biophysical forces, yet the mechanisms governing endothelial cell-cell interactions under different mechanical inputs are not well understood. Using the dorsal longitudinal anastomotic vessel (DLAV) in zebrafish as a model, we studied the roles of multiple biophysical inputs and cerebral cavernous malformation (CCM)-related genes in angiogenesis. Our research identifies heg1 and krit1 (ccm1) as crucial for the formation of endothelial cell-cell interfaces during anastomosis. In mutants of these genes, cell-cell interfaces are entangled with fragmented apical domains. A Heg1 live reporter demonstrated that Heg1 is dynamically involved in the oscillatory constrictions along cell-cell junctions, whilst a Myosin live reporter indicated that heg1 and krit1 mutants lack actomyosin contractility along these junctions. In wild-type embryos, the oscillatory contractile forces at junctions refine endothelial cell-cell interactions by straightening junctions and eliminating excessive cell-cell interfaces. Conversely, in the absence of junctional contractility, the cell-cell interfaces become entangled and prone to collapse in both mutants, preventing the formation of a continuous luminal space. By restoring junctional contractility via optogenetic activation of RhoA, contorted junctions are straightened and disentangled. Additionally, haemodynamic forces complement actomyosin contractile forces in resolving entangled cell-cell interfaces in both wild-type and mutant embryos. Overall, our study reveals that oscillatory contractile forces governed by Heg1 and Krit1 are essential for maintaining proper endothelial cell-cell interfaces and thus for the formation of a continuous luminal space, which is essential to generate a functional vasculature.

Dynamical forces drive organ morphology changes during embryonic development.

Organs and tissues must change shape in precise ways during embryonic development to execute their functions. Multiple mechanisms including biochemical signaling pathways and biophysical forces help drive these morphology changes, but it has been difficult to tease apart their contributions, especially from tissue-scale dynamic forces that are typically ignored. We use a combination of mathematical models and in vivo experiments to study a simple organ in the zebrafish embryo called Kupffer's vesicle. Modeling indicates that dynamic forces generated by tissue movements in the embryo produce shape changes in Kupffer's vesicle that are observed during development. Laser ablations in the zebrafish embryo that alter these forces result in altered organ shapes matching model predictions. These results demonstrate that dynamic forces sculpt organ shape during embryo development.

DIPG-40. LONG TERM SURVIVAL OF A 14 YEAR OLD GIRL WITH H3K27M MUTATED DIFFUSE MIDLINE GLIOMA FOLLOWING RADIOTHERAPY AND PROLONGED TUMOR TREATING FIELDS (TTFIELDS) -CASE REPORT

Abstract INTRODUCTION Pediatric diffuse midline H3K27M mutated glioma has a dismal prognosis. Most cases are treated by radiotherapy and oral chemotherapy, with surgical resection having a debatable role in some. Tumor-treating fields (TTFields) is a noninvasive modality in which alternating electrical fields exert biophysical force on charged and polarizable molecules known as dipoles. TTFields has been shown to extend survival for adult patients with newly diagnosed and recurrent GBM, and is FDA approved for these indications. There is sparse data about pediatric patients. CASE REPORT A 14-year-old girl presented with headache and vomiting. A large left thalamic tumor was diagnosed and underwent subtotal resection. Diagnosis was diffuse midline glioma, H3K27M positive, IDH negative. Molecular Panel: Tumor mutation burden low, microsatellite stable. Genomic findings: FGFR1, NF1, H3F3A -K28M, ATRX R666, MAP3K1 She was re-operated due to a fast tumor relapse within a few weeks, prior to radiotherapy, followed with radiotherapy with local field 59Gy. She then received temozolamide (12 months) concomitant with TTfields (Optune, Novocure). TTfields therapy was administered for 5 years without adverse effects and excellent compliance (above 85%). After 5 years, therapy was withheld, and she is now off therapy NED for another 15 months. DISCUSSION Diffuse midline H3K27M glioma harbors a poor prognosis in children. Children refrain from this treatment both for lack of evidence and because of the difficulty in adhering to a regimen that demands carrying a battery of 1.5-2kg all day and shaving all hair every 3 days. Our patient had a high compliance and as she wore a head scarf for religious customs, the device was not visible. To our knowledge this is the first pediatric reported case of long-term survival of H3K27mutatted midline glioma using TTFields. Further pediatric studies are warranted.

Anodization as a scalable nanofabrication method to engineer mechanobactericidal nanostructures on complex geometries.

Bacterial contamination of implant surfaces is one of the primary causes of their failure, and this threat has been further exacerbated due to the emergence of drug-resistant bacteria. Nanostructured mechanobactericidal surfaces that neutralize bacteria via biophysical forces instead of traditional biochemical routes have emerged as a potential remedy against this issue. Here, we report on the bactericidal activity of titania nanotubes (TNTs) prepared by anodization, a well-established and scalable method. We investigate the differences in bacterial behavior between three different topographies and demonstrate the applicability of this technique on complex three-dimensional (3D) geometries. It was found that the metabolic activity of bacteria on such surfaces was lower, indicative of disturbed intracellular processes. The differences in deformations of the cell wall of Gram-negative and positive bacteria were investigated from electron micrographs Finally, nanoindentation experiments show that the nanotubular topography was durable enough against forces typically experienced in daily life and had minimal deformation under forces exerted by bacteria. Our observations highlight the potential of the anodization technique for fabricating mechanobactericidal surfaces for implants, devices, surgical instruments, and other surfaces in a healthcare setting in a cheap, scalable way.

Assessment of human embryonic stem cells differentiation into definitive endoderm lineage on the soft substrates.

Pluripotent stem cells (PSCs) hold enormous potential for treating multiple diseases owing to their ability to self-renew and differentiate into any cell type. Albeit possessing such promising potential, controlling their differentiation into a desired cell type continues to be a challenge. Recent studies suggest that PSCs respond to different substrate stiffness and, therefore, can differentiate towards some lineages via Hippo pathway. Human PSCs can also differentiate and self-organize into functional cells, such as organoids. Traditionally, human PSCs are differentiated on stiff plastic or glass plates towards definitive endoderm and then into functional pancreatic progenitor cells in the presence of soluble growth factors. Thus, whether stiffness plays any role in differentiation towards definitive endoderm from human pluripotent stem cells(hPSCs) remains unclear. Our study found that the directed differentiation of human embryonic stem cells towards endodermal lineage on the varying stiffness did not differ from the differentiation on stiff plastic dishes. We also observed no statistical difference between the expression of yes-associated protein(YAP) and phosphorylatedYAP. Furthermore, we demonstrate that lysophosphatidic acid, a YAP activator, enhanced definitive endoderm formation, whereas verteporfin, a YAP inhibitor, did not have the significant effect on the differentiation. In summary, our results suggest that human embryonic stem cells may not differentiate in response to changes in stiffness, and that such cues may not have as significant impact on the level of YAP. Our findings indicate that more research is needed to understand the direct relationship between biophysical forces and hPSCs differentiation.

Alternating Conditional Expectations: Introducing a Non‐Parametric Statistical Method to Interpret Long‐Term Greenhouse Gas Flux Measurements Over Semi‐Arid and Wetland Ecosystems

AbstractWe explore the potential of using a non‐parametric statistical method called Alternating Conditional Expectations, ACE, to quantify functional relationships in biogeosciences. Here, ACE is used to quantify the non‐linear and multi‐faceted responses of greenhouse gas fluxes to a set of biophysical forcings, when the shapes of those response surfaces are unknown. We evaluated the statistical method over two contrasting ecosystems and two contrasting time steps. One case involved quantifying the biophysical controls of water vapor and carbon dioxide (CO2) fluxes over a semi‐arid oak savanna using daily integrated fluxes. The other case evaluated the responses of CO2 and methane (CH4) flux measurements to a set of biophysical forcings at a restored tidal wetland using thirty‐minute averages. The statistical model, based on 4 independent variables, explained up over 90% of the variation in daily integrated flux densities of water vapor and net carbon dioxide exchange at the savanna site. This fit was defined by distinct non‐linear responses to such drivers as gross primary production, photosynthetically active radiation, air temperature, vapor pressure deficit and soil moisture. At the tidal wetland site, we evaluated net carbon dioxide and methane fluxes with short‐term measurements to capture the influence of rising and falling tides and seasonality in biological activity. The statistical model defined the shape of the forcing of fluxes due to the roles of carbon exudates, water table depth, oxygen level in the water column, temperature and vegetation status. The statistical fits of the greenhouse gas fluxes were less precise than the savanna case. The fetch varies on a run‐to‐run basis as it is comprised of a heterogeneous mosaic of open water and vegetation. Furthermore, it is difficult to monitor the environmental conditions of the archaea and bacteria in the sediments that produce methane and carbon dioxide.

Effective cell membrane tension protects red blood cells against malaria invasion.

A critical step in how malaria parasites invade red blood cells (RBCs) is the wrapping of the membrane around the egg-shaped merozoites. Recent experiments have revealed that RBCs can be protected from malaria invasion by high membrane tension. While cellular and biochemical aspects of parasite actomyosin motor forces during the malaria invasion have been well studied, the important role of the biophysical forces induced by the RBC membrane-cytoskeleton composite has not yet been fully understood. In this study, we use a theoretical model for lipid bilayer mechanics, cytoskeleton deformation, and membrane-merozoite interactions to systematically investigate the influence of effective RBC membrane tension, which includes contributions from the lipid bilayer tension, spontaneous tension, interfacial tension, and the resistance of cytoskeleton against shear deformation on the progression of membrane wrapping during the process of malaria invasion. Our model reveals that this effective membrane tension creates a wrapping energy barrier for a complete merozoite entry. We calculate the tension threshold required to impede the malaria invasion. We find that the tension threshold is a nonmonotonic function of spontaneous tension and undergoes a sharp transition from large to small values as the magnitude of interfacial tension increases. We also predict that the physical properties of the RBC cytoskeleton layer-particularly the resting length of the cytoskeleton-play key roles in specifying the degree of the membrane wrapping. We also found that the shear energy of cytoskeleton deformation diverges at the full wrapping state, suggesting the local disassembly of the cytoskeleton is required to complete the merozoite entry. Additionally, using our theoretical framework, we predict the landscape of myosin-mediated forces and the physical properties of the RBC membrane in regulating successful malaria invasion. Our findings on the crucial role of RBC membrane tension in inhibiting malaria invasion can have implications for developing novel antimalarial therapeutic or vaccine-based strategies.

Pyrosociality

Abstract Pyrosociality is a framework for theorizing the simultaneous production of forests and fires while discerning who is powerful and who is vulnerable in multispecies encounters mediated by fire. This article reviews literature about fire science and situates academic dialogue about the ecological consequences of social processes within real-world goings-on in the Blue Ridge Mountains. Pyrosocial theory draws from posthumanism, science and technology studies, and feminist anthropology to assess fire management. Qualitative data from properties managed by the Nantahala- Pisgah National Forests, North Carolina Forest Service, and South Carolina Forestry Commission ground pyrosocial theory in shifting ideas and practices related to excluding, suppressing, fostering, and igniting fires. When centering fire, what facts, truths, complexities, and subtleties come to light? The pyrosocial approach reveals pyropower, or individual variabilities and structural hierarchies related to controlling or influencing more-than-human communities. Focusing on power and vulnerability within habitats co-constructed by multispecies agents and biophysical forces accentuates meaningful relationships.

Emerging Trends in Nanomaterial-Based Biomedical Aspects

Comprehending the interfacial interaction of nanomaterials (NMs) and biological systems is a significant research interest. NMs comprise various nanoparticles (NPs) like carbon nanotubes, graphene oxides, carbon dots, graphite nanopowders, etc. These NPs show a variety of interactions with biological interfaces via organic layers, therapeutic molecules, proteins, DNA, and cellular matrices. A number of biophysical and colloidal forces act at the morphological surface to regulate the biological responses of bio-nanoconjugates, imparting distinct physical properties to the NMs. The design of future-generation nano-tools is primarily based on the basic properties of NMs, such as shape, size, compositional, functionality, etc., with studies being carried out extensively. Understanding their properties promotes research in the medical and biological sciences and improves their applicability in the health management sector. In this review article, in-depth and critical analysis of the theoretical and experimental aspects involving nanoscale material, which have inspired various biological systems, is the area of focus. The main analysis involves different self-assembled synthetic materials, bio-functionalized NMs, and their probing techniques. The present review article focuses on recent emerging trends in the synthesis and applications of nanomaterials with respect to various biomedical applications. This article provides value to the literature as it summarizes the state-of-the-art nanomaterials reported, especially within the health sector. It has been observed that nanomaterial applications in drug design, diagnosis, testing, and in the research arena, as well as many fatal disease conditions like cancer and sepsis, have explored alongwith drug therapies and other options for the delivery of nanomaterials. Even the day-to-day life of the synthesis and purification of these materials is changing to provide us with a simplified process. This review article can be useful in the research sector as a single platform wherein all types of nanomaterials for biomedical aspects can be understood in detail.

Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals.

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering. Leveraging this programmable crystal, we determined 28 biomolecular structures to capture mmDNA reactions. We found that silver(I) binds with increasing occupancy in T-T and U-U pairs at elevated pH levels, and we exploited this to capture silver(I) and mercury(II) within the same base pair and to isolate the titration points for homo- and heterometal base pair modes. We additionally determined the structure of a C-C pair with both silver(I) and mercury(II). Finally, we extend our paradigm to capture cadmium(II) in T-T pairs together with mercury(II) at high pH. The precision self-assembly of heterobimetallic DNA chemistry at the sub-nanometer scale will enable atomistic design frameworks for more elaborate mmDNA-based nanodevices and nanotechnologies.

Nuclear mechanosignaling in striated muscle diseases.

Mechanosignaling describes processes by which biomechanical stimuli are transduced into cellular responses. External biophysical forces can be transmitted via structural protein networks that span from the cellular membrane to the cytoskeleton and the nucleus, where they can regulate gene expression through a series of biomechanical and/or biochemical mechanosensitive mechanisms, including chromatin remodeling, translocation of transcriptional regulators, and epigenetic factors. Striated muscle cells, including cardiac and skeletal muscle myocytes, utilize these nuclear mechanosignaling mechanisms to respond to changes in their intracellular and extracellular mechanical environment and mediate gene expression and cell remodeling. In this brief review, we highlight and discuss recent experimental work focused on the pathway of biomechanical stimulus propagation at the nucleus-cytoskeleton interface of striated muscles, and the mechanisms by which these pathways regulate gene regulation, muscle structure, and function. Furthermore, we discuss nuclear protein mutations that affect mechanosignaling function in human and animal models of cardiomyopathy. Furthermore, current open questions and future challenges in investigating striated muscle nuclear mechanosignaling are further discussed.

Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate

Lungs undergo mechanical strain during breathing, but how these biophysical forces affect cell fate and tissue homeostasis are unclear. We show that biophysical forces through normal respiratory motion actively maintain alveolar type 1 (AT1) cell identity and restrict these cells from reprogramming into AT2 cells in the adult lung. AT1 cell fate is maintained at homeostasis by Cdc42- and Ptk2-mediated actin remodeling and cytoskeletal strain, and inactivation of these pathways causes a rapid reprogramming into the AT2 cell fate. This plasticity induces chromatin reorganization and changes in nuclear lamina-chromatin interactions, which can discriminate AT1 and AT2 cell identity. Unloading the biophysical forces of breathing movements leads to AT1-AT2 cell reprogramming, revealing that normal respiration is essential to maintain alveolar epithelial cell fate. These data demonstrate the integral function of mechanotransduction in maintaining lung cell fate and identifies the AT1 cell as an important mechanosensor in the alveolar niche.

Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis

The integrity of the structure and function of the endometrium is essential for the maintenance of fertility. However, the repair mechanisms of uterine injury remain largely unknown. Here, we showed that the disturbance of mechanical cue homeostasis occurs after uterine injury. Applying a multimodal approach, we identified YAP as a sensor of biophysical forces that drives endometrial regeneration. Through protein activation level analysis of the combinatorial space of mechanical force strength and of the presence of particular kinase inhibitors and gene silencing reagents, we demonstrated that mechanical cues related to extracellular matrix rigidity can turn off the Rap1a switch, leading to the inactivation of ARHGAP35and then induced activation of RhoA, which in turn depends on the polymerization of the agonist protein F-actin to activate YAP. Further study confirmed that mechanotransduction significantly accelerates remodeling of the uterus by promoting the proliferation of endometrial stromal cells in vitro and in vivo. These studies provide new insights into the dynamic regulatory mechanisms behind uterine remodeling and the function of mechanotransduction.B4ojxzzgfZhteej7Gc57h4Video

Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells.

Gastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes-associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY-box transcription factor 17 (SOX17)+ T/BRACHYURY+ cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction-coupled wingless-type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts.

Flow-Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes.

Background Lipoprotein lipase (LPL)-derived fatty acid is a major source of energy for cardiac contraction. Synthesized in cardiomyocytes, LPL requires translocation to the vascular lumen for hydrolysis of lipoprotein triglyceride, an action mediated by endothelial cell (EC) release of heparanase. We determined whether flow-mediated biophysical forces can cause ECs to secrete heparanase and thus regulate cardiac metabolism. Methods and Results Isolated hearts were retrogradely perfused. Confluent rat aortic ECs were exposed to laminar flow using an orbital shaker. Cathepsin L activity was determined using gelatin-zymography. Diabetes was induced in rats with streptozotocin. Despite the abundance of enzymatically active heparanase in the heart, it was the enzymatically inactive, latent heparanase that was exceptionally responsive to flow-induced release. EC exposed to orbital rotation exhibited a similar pattern of heparanase secretion, an effect that was reproduced by activation of the mechanosensor, Piezo1. The laminar flow-mediated release of heparanase from EC required activation of both the purinergic receptor and protein kinase D, a kinase that assists in vesicular transport of proteins. Heparanase influenced cardiac metabolism by increasing cardiomyocyte LPL displacement along with subsequent replenishment. The flow-induced heparanase secretion was augmented following diabetes and could explain the increased heparin-releasable pool of LPL at the coronary lumen in these diabetic hearts. Conclusions ECs sense fluid shear-stress and communicate this information to subjacent cardiomyocytes with the help of heparanase. This flow-induced mechanosensing and its dynamic control of cardiac metabolism to generate ATP, using LPL-derived fatty acid, is exquisitely adapted to respond to disease conditions, like diabetes.

Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation.

Over the decades, conventional in vitro culture systems and animal models have been used to study physiology, nutrient or drug metabolisms including mechanical and physiopathological aspects. However, there is an urgent need for Integrated Testing Strategies (ITS) and more sophisticated platforms and devices to approach the real complexity of human physiology and provide reliable extrapolations for clinical investigations and personalized medicine. Organ-on-a-chip (OOC), also known as a microphysiological system, is a state-of-the-art microfluidic cell culture technology that sums up cells or tissue-to-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology, and it has been developed to fill the gap between in vitro experimental models and human pathophysiology. The wide range of OOC platforms involves the miniaturization of cell culture systems and enables a variety of novel experimental techniques. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living biosystems, the development of vascular structure is the salient feature common to almost all organ-on-a-chip platforms. Herein, we provide a snapshot of this fast-evolving sophisticated technology. We will review cutting-edge developments and advances in the OOC realm, discussing current applications in the biomedical field with a detailed description of how this technology has enabled the reconstruction of complex multi-scale and multifunctional matrices and platforms (at the cellular and tissular levels) leading to an acute understanding of the physiopathological features of human ailments and infections in vitro.

What Counts—Why Growth Economics is Failing Us

A rapidly growing body of research suggests that modern economies find themselves at existential crossroads: both prosperity and survival are a function of consumption-fueled economic growth. Prosperity seemingly depends on it; survival is made increasingly impossible by it. Economists measure economic growth by what is generally recognized as a deeply flawed yet still hegemonic economic performance indicator—GDP. This paper suggests that growth based in increased consumption is in need of reconceptualization no matter what the measure, and invites the research community of the Journal of Consumer Culture to investigate what such a research agenda might look like. Economic logic itself, this essay argues, needs to be re-embedded in science, rather than operate as a self-referential logic outside of natural boundaries. Biophysical limits force us to question economic growth as a goal. A wide range of social pathologies, furthermore, from inequality to stress to loneliness, raise deep questions about the desirability of growth. The essay is a self-conscious provocation to the discipline of economics: there is an emerging need to move beyond a conceptualization of the economy as a self-contained system of monetary market exchanges defining the relations between production, distribution, and consumption.

Space Biomedicine: A Unique Opportunity to Rethink the Relationships between Physics and Biology.

Space biomedicine has provided significant technological breakthroughs by developing new medical devices, diagnostic tools, and health-supporting systems. Many of these products are currently in use onboard the International Space Station and have been successfully translated into clinical practice on Earth. However, biomedical research performed in space has disclosed exciting, new perspectives regarding the relationships between physics and medicine, thus fostering the rethinking of the theoretical basis of biology. In particular, these studies have stressed the critical role that biophysical forces play in shaping the function and pattern formation of living structures. The experimental models investigated under microgravity conditions allow us to appreciate the complexity of living organisms through a very different perspective. Indeed, biological entities should be conceived as a unique magnification of physical laws driven by local energy and order states overlaid by selection history and constraints, in which the source of the inheritance, variation, and process of selection has expanded from the classical Darwinian definition. The very specific nature of the field in which living organisms behave and evolve in a space environment can be exploited to decipher the underlying, basic processes and mechanisms that are not apparent on Earth. In turn, these findings can provide novel opportunities for testing pharmacological countermeasures that can be instrumental for managing a wide array of health problems and diseases on Earth.

Investigating biophysical control of marine phytoplankton dynamics via Bayesian mechanistic modeling

Marine phytoplankton possess a key position in multiple ecological, biological, and environmental processes; therefore, constructing a systematic and comprehensive mechanistic understanding of the leading mechanisms and key biophysical drivers of phytoplankton dynamics is crucial for evaluating biophysical forcings and ecological responses. Here, we develop a process-based model to improve the characterization of controlling mechanisms and assess the relative importance of nutrients, light, temperature, and oceanic mixing for explaining chlorophyll-a variability in the western North Pacific Ocean. The model is calibrated using 20-year observational data of chlorophyll-a concentrations from 1993 to 2012 in a Bayesian framework to provide data-driven inference and a rigorous uncertainty quantification of important biophysical rates. The model explains approximately 61% of the variability in chlorophyll-a. Our results, supported by cross-validation, show that the chlorophyll-a concentration is much more responsive to temperature variability than nutrients, light, or mixing. By synthesizing the effects of multiple nutrients (i.e., nitrogen, phosphorus, silica, and iron) on phytoplankton dynamics, we find that iron and nitrogen largely determine the chlorophyll-a variability. Sensitivity analysis shows that future warming conditions with +3°C change in temperature will impede phytoplankton production by 24% due to an intensified phytoplankton mortality impact. Our findings highlight the potential of “deductive-and-inductive” modeling approaches combining embedded biophysical mechanisms and probabilistic uncertainty quantification to effectively integrate and leverage sporadic ocean monitoring efforts and ultimately improve the marine water quality predictions.

Local extensional flows promote long-range fiber alignment in 3D collagen hydrogels

Randomly oriented type I collagen (COL1) fibers in the extracellular matrix are reorganized by biophysical forces into aligned domains extending several millimeters and with varying degrees of fiber alignment. These aligned fibers can transmit traction forces, guide tumor cell migration, facilitate angiogenesis, and influence tissue morphogenesis. To create aligned COL1 domains in microfluidic cell culture models, shear flows have been used to align thin COL1 matrices (<50 µm in height) in a microchannel. However, there has been limited investigation into the role of shear flows in aligning 3D hydrogels (>130 µm). Here, we show that pure shear flows do not induce fiber alignment in 3D atelo COL1 hydrogels, but the simple addition of local extensional flow promotes alignment that is maintained across several millimeters, with a degree of alignment directly related to the extensional strain rate. We further advance experimental capabilities by addressing the practical challenge of accessing a 3D hydrogel formed within a microchannel by introducing a magnetically coupled modular platform that can be released to expose the microengineered hydrogel. We demonstrate the platform’s capability to pattern cells and fabricate multi-layered COL1 matrices using layer-by-layer fabrication and specialized modules. Our approach provides an easy-to-use fabrication method to achieve advanced hydrogel microengineering capabilities that combine fiber alignment with biofabrication capabilities.