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Kim, S. K.

Publications and source records attributed to Kim, S. K..

At least 19 recordsLinked to original sources

Learning fly pose from vision-language annotations

Animal pose estimation typically requires manual annotation of body parts to train neural networks for each new recording system or environmental condition. Here we use a general-purpose vision-language model (VLM) to generate annotations in multi-animal recordings of fruit flies (Drosophila melanogaster). Initial annotations follow written anatomical descriptions and are reviewed by an independent VLM session using neighboring video frames. On 120 held-out fly images, AI annotations had a median distance of 2.28 pixels from human labels, with 84.0% agreement within eight pixels, averaged across landmark types. The comparison included 10 landmarks, with head and eyes analyzed separately because of systematic differences in placement. Review improved agreement primarily at the feet, with the largest remaining discrepancies at positions with limited visual evidence. Visual inspection revealed cases in which the AI annotations were more anatomically accurate than those of an experienced human annotator, particularly at the feet. A convolutional network trained using SLEAP on 300 AI-annotated fly images showed similar agreement with human labels and closely reproduced the AI annotations on held-out images, with a median distance of 1.56 pixels. We also applied the procedure to recordings from another laboratory, using new AI annotations to train a separate pose network. Although VLM annotation required minutes per fly, the trained networks enabled pose estimation throughout more than 700,000 frames. These results demonstrate that VLM annotations can support fast animal pose estimation without manually labeled training images.

animal behavior and cognition↗

Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells

Pancreatic islet {beta} cells integrate glucose and hormonal cues to control insulin secretion through spatially and temporally organized phosphorylation networks in health and diabetes. Here, using Metabolic STAMP (Synchronized Temporal-Spatial Analysis via Microscopy and Phosphoproteomics), we combine time-resolved phosphoproteomics, imaging, and kinase inhibition in mouse {beta} cells and human islets to map stimulus-specific GPCR signaling pathways. Metabolic STAMP reveals that GLP1-R and FFAR4 engage distinct, compartmentalized kinase programs, including GLP1-R-biased ERK activation, receptor-specific cAMP-PKA domains, and a phospho-ATAT1/HDAC6 node that differentially modulates microtubule acetylation and insulin secretion during GSIS based on stimulation conditions. These GPCR-responsive phospho-signatures and microtubule remodeling patterns are substantially conserved in human islets. Together, our data define an integrated, compartmentalized signaling architecture linking metabolic GPCR inputs, organelle remodeling, and insulin secretion, and provide a {beta}-cell phosphoproteomic resource that connects dynamic signaling nodes to human genetic risk and potential therapeutic targets.

physiology↗

Curing autoimmune diabetes with islet and hematopoietic cell transplantation after CD117 antibody-based conditioning

Mixed hematopoietic chimerism after allogeneic hematopoietic cell transplantation (HCT) promotes tolerance of transplanted donor-matched solid organs, corrects autoimmunity, and could transform therapeutic strategies for autoimmune type 1 diabetes (T1D). However, development of non-toxic bone marrow conditioning protocols is needed to expand clinical use. We developed a chemotherapy-free, non-myeloablative (NMA) conditioning regimen that achieves mixed chimerism and allograft tolerance across MHC barriers in NOD mice. We obtained durable mixed hematopoietic chimerism in prediabetic NOD mice using anti-c-Kit monoclonal antibody, T-cell depleting antibodies, JAK1/2 inhibition, and low-dose total body irradiation prior to transplantation of MHC-mismatched B6 hematopoietic cells, preventing diabetes in 100% of chimeric NOD:B6 mice. In overtly diabetic NOD mice, NMA conditioning followed by combined B6 HCT and islet transplantation durably corrected diabetes in 100% of chimeric mice without chronic immunosuppression or graft-versus-host disease (GVHD). Chimeric mice remained immunocompetent, as assessed by blood count recovery and rejection of 3rd party allogeneic islets. Adoptive transfer studies and analysis of autoreactive T cells confirmed correction of autoimmunity. Analysis of chimeric NOD mice revealed central thymic deletion and peripheral tolerance mechanisms. Thus, with NMA conditioning and cell transplantation, we achieved durable hematopoietic chimerism without GVHD, promoted islet allograft tolerance, and reversed established T1D. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/673576v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@23fcdorg.highwire.dtl.DTLVardef@1aac97borg.highwire.dtl.DTLVardef@191e06forg.highwire.dtl.DTLVardef@25be2b_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes

Mixed hematopoietic chimerism after hematopoietic cell transplantation (HCT) can modulate the immune system and induce tolerance to allogeneic tissues. However, bone marrow conditioning-related toxicities preclude wider adoption of HCT for transplant allotolerance. We sought agents that reduced conditioning intensity, while promoting durable mixed chimerism after HCT across complete major histocompatibility complex (MHC) mismatch in diabetic mice, permitting islet allotransplantation and diabetes reversal. We systematically tested baricitinib (JAK1/2 inhibitor), venetoclax (Bcl2 inhibitor), and CD47 antibody, agents in current clinical use, and quantified hematopoietic chimerism after HCT. Combined with CD117 antibody, transient T cell depletion, and just 10 centigray (cGy) total body irradiation (TBI), these agents enabled durable mixed chimerism and matching allo-islet tolerance, to cure diabetes without evidence of GVHD. Thus, we have developed a conditioning regimen to promote allogeneic mixed hematopoietic chimerism and transplanted islet allotolerance that minimizes conditioning radiation and cures diabetes, a significant achievement.

immunology↗

Adaptive Evolution of Gene Regulatory Networks in Mammalian Neocortical Neurons

Mammals have evolved a plethora of adaptations that have enabled them to thrive in diverse environments. Among the most significant is the emergence of a more complex brain, exemplified by the dramatic transformation of the dorsal cortex from a single layer of excitatory projection neurons (ExNs) in ancestors to a multilayered cerebral neocortex enriched with diverse intratelencephalic (IT) and extratelencephalic (ET) ExN subtypes. These ExNs established specialized projection systems, such as the corticospinal tract and corpus callosum, enhancing brain connectivity and functionality. However, the evolutionary mechanisms underlying these mammalian-specific adaptations remain elusive. By comparing the landscape of gene expression and cis-regulatory elements (CREs) in mouse ExN subtypes and by cross-species examination of mammalian and non-mammalian CREs, we identified mammalian-specific CREs and expression patterns. The mammalian-specific CREs include a subset bound by ZBTB18 that are associated with genes defining IT and ET subtypes and connectivity. Both ZBTB18 and these target genes have previously been implicated in intellectual disability and autism. Deletion of Zbtb18 in mouse ExNs dysregulated target gene expression, reduced molecular diversity, diminished corticospinal and callosal projections, and increased intrahemispheric cortico-cortical association projections to the prefrontal cortex, resembling features of non-mammalian dorsal pallium. Interestingly, ZBTB18 binding motifs are highly enriched in callosally projecting IT-biased CREs, where they show higher conservation specifically in mammals. This study uncovers critical components and mammalian-specific evolutionary adaptations within a regulatory node essential for neocortical ExN identity and connectivity, with implications for neurodevelopmental and neuropsychiatric disorders.

neuroscience↗

EB-SUN, a New Microtubule Plus-End Tracking Protein in Drosophila.

Microtubule (MT) regulation is essential for oocyte development. In Drosophila, MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins (MAPs) that regulate MTs in the Drosophila ovary, we identified a previously uncharacterized gene, CG18190, encoding a novel MT end-binding (EB) protein, which we propose to name EB-SUN. We show that EB-SUN colocalizes with EB1 at growing microtubule plus-ends in Drosophila S2 cells. Tissue-specific and developmental expression profiles from Paralog Explorer reveal that EB-SUN is predominantly expressed in the ovary and early embryos, while EB1 is ubiquitously expressed. Furthermore, as early as oocyte determination, EB-SUN comets are highly concentrated in oocytes during oogenesis. EB-SUN knockout (KO) results in a decrease in MT density at the onset of mid-oogenesis (Stage 7) and delays oocyte growth during late mid-oogenesis (Stage 9). Combining EB-SUN KO with EB1 knockdown (KD) in germ cells significantly further reduced MT density at Stage 7. Notably, all eggs from EB-SUN KO/EB1 KD females fail to hatch, unlike single gene depletion, suggesting a functional redundancy between these two EB proteins during embryogenesis. Our findings indicate that EB-SUN and EB1 play distinct roles during early embryogenesis. Significance StatementO_LIOur study identified a novel microtubule end-binding (EB) protein, which is highly expressed in the Drosophila ovary, and we propose to name it EB-SUN. C_LIO_LIWe demonstrate the functional redundancy of EB-SUN and EB1 during oocyte development, while highlighting their distinct roles in early embryogenesis. C_LIO_LIGiven the high conservation of MT-dependent mechanisms in oogenesis and EB proteins across species, these findings provide insights into the differential regulation and tissue-specific functions of the EB family, using Drosophila as a model system, potentially benefiting future research on MT regulation in higher organisms. C_LI

cell biology↗

Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression

Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of homeostasis, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment. Statement of significanceBy analyzing transcriptional programs in healthy and tumor-associated pancreatic mesenchyme, we find that a sub-population of mesenchymal cells in healthy pancreas tissue express the paracrine signaling factor KITL. Loss of mesenchymal KITL is an accompanying and permissive feature of pancreas tumor evolution, with potential implications for cancer interception.

cancer biology↗

CRISPR/Cas9 gene editing in Drosophila via visual selection in a summer classroom

CRISPR/Cas9 methods are a powerful in vivo approach to edit the genome of Drosophila melanogaster. To convert existing Drosophila GAL4 lines to LexA driver lines in a secondary school classroom setting, we applied the CRISPR-based genetic approach to a collection of Gal4 driver lines. The integration of the yellow+ coat color marker into homology-assisted CRISPR knock-in (HACK) enabled visual selection of Gal4-to-LexA conversions using brightfield stereo-microscopy available in a broader set of standard classrooms. Here, we report the successful conversion of eleven Gal4 lines with expression in neuropeptide-expressing cells into corresponding, novel LexA drivers. The conversion was confirmed by LexA- and Gal4-specific GFP reporter gene expression. This curriculum was successfully implemented in a summer course running 16 hours/week for seven weeks. The modularity, flexibility, and compactness of this course should enable development of similar classes in secondary schools and undergraduate curricula, to provide opportunities for experience-based science instruction, and university-secondary school collaborations that simultaneously fulfill research needs in the community of science.

genetics↗

Multiplexed CRISPR gene editing in primary human islet cells with Cas9 ribonucleoprotein

Successful genome editing in primary human islets could reveal features of the genetic regulatory landscape underlying {beta} cell function and diabetes risk. Here, we describe a CRISPR-based strategy to interrogate functions of predicted regulatory DNA elements using electroporation of a complex of Cas9 ribonucleoprotein (Cas9 RNP) and guide RNAs into primary human islet cells. We successfully targeted coding regions including the PDX1 exon 1, and non-coding DNA linked to diabetes susceptibility. CRISPR/Cas9 RNP approaches revealed genetic targets of regulation by DNA elements containing candidate diabetes risk SNPs, including an in vivo enhancer of the MPHOSPH9 gene. CRISPR/Cas9 RNP multiplexed targeting of two cis-regulatory elements linked to diabetes risk in PCSK1, which encodes an endoprotease crucial for insulin processing, also demonstrated efficient simultaneous editing of PCSK1 regulatory elements, resulting in impaired {beta} cell PCSK1 regulation and insulin secretion. Multiplex CRISPR/Cas9 RNP provides powerful approaches to investigate and elucidate human islet cell gene regulation in health and diabetes.

cell biology↗

CRISPR/Cas9 gene editing to generate Drosophila LexA lines in secondary school classes

Genome editing in vivo with CRISPR/Cas9 generates powerful tools to study gene regulation and function. We developed CRISPR-based methods that permitted secondary school student scientists to convert Drosophila GAL4 lines to LexA lines. Our novel curricula implement a new donor strain optimizing Homology-assisted CRISPR knock-in (HACK) that simplifies screening using light microscopy. Successful curricula adoption by a consortium of schools led to the generation and characterization of 16 novel LexA lines. This includes extensive comparative tissue expression analysis between the parental Gal4 and derived LexA lines. From this collaboration, we established a workflow to systematically generate LexA lines from frequently-used GAL4 lines. Modular courses developed from this effort can be tailored to specific secondary school scheduling needs, and serve as a template for science educators to innovate courses and instructional goals. Our unique collaborations highlight that resources and expertise harnessed by university-based research laboratories can transform experiential science instruction in secondary schools while addressing research needs for the community of science.

genetics↗

Structure and dynamics of the essential endogenous mycobacterial polyketide synthasePks13

Mycobacterium tuberculosis is currently the leading cause of death by any bacterial infection1. The mycolic acid layer of the cell wall is essential for viability and virulence, and the enzymes responsible for its synthesis are therefore front line targets for antimycobacterial drug development2,3. Polyketide synthase 13 (Pks13) is a module comprised of a closely symmetric parallel dimer of chains, each encoding several enzymatic and transport functions, that carries out the condensation of two different very long chain fatty acids to produce mycolic acids that are essential components of the mycobacterial cell wall. Consequently individual enzymatic domains of Pks13 are targets for antimycobacterial drug development4. To understand this machinery, we sought to determine the structure and domain trajectories of the dimeric multi-enzyme Pks13, a 2x198,426 Dalton complex, from protein purified endogenously from mycobacteria under normal growth conditions, to capture it with normal substrates bound trapped in action. Structures of the multi-domain assembly revealed by cryogenic electron microscopy (cryoEM) define the ketosynthase (KS), linker, and acyltransferase (AT) domains, each at atomic resolution (1.8[A]), with bound substrates defined at 2.4[A] and 2.9[A] resolution. Image classification reveals two distinct structures with alternate locations of the N-terminal acyl carrier protein (termed ACP1a, ACP1b) seen at 3.6[A] and 4.6[A] resolution respectively. These two structures suggest plausible intermediate states, related by a ~60[A] movement of ACP1, on the pathway for substrate delivery from the fatty acyl-ACP ligase (FadD32) to the ketosynthase domain. The linking sequence between ACP1 and the KS includes an 11 amino acid sequence with 6 negatively charged side chains that lies in different positively charged grooves on the KS in ACP1a versus ACP1b structures. This charge complementarity between the extended chain and the grooves suggests some stabilization of these two distinct orientations. Other domains are visible at lower resolution and indicate flexibility relative to the KS-AT core. The chemical structures of three bound endogenous long chain fatty acid substrates with their proximal regions defined in the structures were determined by electrospray ionization mass spectrometry. The domain proximities were probed by chemical cross-linking and identified by mass spectrometry. These were incorporated into integrative structure modeling to define multiple domain configurations that transport the very long fatty acid chains throughout the multistep Pks13 mediated synthetic pathway.

biochemistry↗

Bidirectional multiciliated cell extrusion is controlled by Notch driven basal extrusion and Piezo 1 driven apical extrusion.

Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late stage development there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function. Normal cell extrusion is typically unidirectional whereas bidirectional extrusion is often associated with disease (e.g. cancer). We describe two distinct mechanisms for MCC extrusion, a basal extrusion driven by Notch signaling and an apical extrusion driven by Piezo1. Early in the process there is a strong bias towards basal extrusion, but as development continues there is a shift towards apical extrusion. Importantly, receptivity to the Notch signal is age-dependent and governed by the maintenance of the MCC transcriptional program such that extension of this program is protective against cell loss. In contrast, later apical extrusion is regulated by Piezo 1 such that premature activation of Piezo 1 leads to early extrusion while blocking Piezo 1 leads to MCC maintenance. Distinct mechansms for MCC loss underlie the importance of their removal during epithelial remodeling. Summay StatementCell extrusion typically occurs unidirectionally. We have identified a single population of multiciliated cells that extrudes bidirectionally: Notch-driven basal extrusion and Piezo 1-mediated apical extrusion.

cell biology↗

Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes

Altered function and gene regulation of pancreatic islet beta cells is a hallmark of type 2 diabetes (T2D), but a comprehensive understanding of mechanisms driving T2D is still missing. Here we integrate information from measurements of chromatin activity, gene expression and function in single beta cells with genetic association data to identify disease-causal gene regulatory changes in T2D. Using machine learning on chromatin accessibility data from 34 non-diabetic, pre-T2D and T2D donors, we robustly identify two transcriptionally and functionally distinct beta cell subtypes that undergo an abundance shift in T2D. Subtype-defining active chromatin is enriched for T2D risk variants, suggesting a causal contribution of subtype identity to T2D. Both subtypes exhibit activation of a stress-response transcriptional program and functional impairment in T2D, which is likely induced by the T2D-associated metabolic environment. Our findings demonstrate the power of multimodal single-cell measurements combined with machine learning for identifying mechanisms of complex diseases.

systems biology↗

Shadow imaging for panoptical visualisation of living brain tissue

Progress in neuroscience research hinges on technical advances in visualizing living brain tissue with high fidelity and facility. Current neuroanatomical imaging approaches either require tissue fixation, do not have cellular resolution or only give a fragmented view. Here, we show how regular light microscopy together with fluorescence labeling of the interstitial fluid in the extracellular space provide comprehensive optical access in real-time to the anatomical complexity and dynamics of living brain tissue.

neuroscience↗

30-Minute Highly Multiplexed VaxArray Immunoassay for Pneumococcal Vaccine Antigen Characterization

Pneumonia accounts for over 20% of deaths worldwide in children aged 1 to 5 years, disproportionately affecting lower- and middle-income countries. Effective, highly multivalent pneumococcal vaccines are available to decrease disease burden, with numerous new vaccines currently under development to serve a variety of worldwide markets. However, pneumococcal conjugate vaccines are among the hardest biologics to manufacture and characterize due to their complexity and heterogeneity. Current characterization methods are often inherently singleplex, requiring separate tests for each serotype present. In addition, identity and quantity are often determined with separate methods. We have developed the VaxArray Pneumococcal Assay for applications in identity, quantity, and stability testing of pneumococcal polysaccharide and pneumococcal conjugate vaccines. The VaxArray Pneumococcal Assay has a time to result of less than 30 minutes and is an off-the-shelf multiplexed, microarray-based immunoassay kit that can identify and simultaneously quantify 23 pneumococcal polysaccharide serotypes common to many on-market and in-development vaccines. Here, we highlight the potential of the assay for identity testing by showing high reactivity and serotype-specificity to a wide variety of native polysaccharides, CRM197-conjugated polysaccharides, and drug product. The assay also has vaccine-relevant lower limits of quantification in the low to mid ng/mL range and can be used for accurate quantification even in adjuvanted vaccines. Excellent correlation to the anthrone assay is demonstrated, with VaxArray resulting in significantly improved precision over this antiquated chemical method.

immunology↗

HNF1α transcriptional activation and repression maintain human islet α and β cell function

HNF1A haploinsufficiency underlies the most common form of human monogenic diabetes (HNF1A-MODY) and hypomorphic HNF1A variants confer type 2 diabetes risk, but a lack of experimental systems has limited our understanding of how the transcription factor HNF1 regulates adult human islet function. Here, we combined human islet genetics, RNA sequencing, Cleavage Under Targets & Release Using Nuclease (CUT&RUN) chromatin mapping, patch-clamp electrophysiology and transplantation-based assays to elucidate HNF1-regulated mechanisms in mature pancreatic and {beta} cells. shRNA-mediated suppression of HNF1A in primary human pseudoislets led to blunted insulin output and dysregulated glucagon secretion both in vitro and after transplantation into immunocompromised mice, recapitulating phenotypes observed in HNF1A-MODY patients. These deficits corresponded with altered expression of genes encoding factors critical for hormone secretion, including calcium channel subunits, ATP-transporters and extracellular matrix constituents. Additionally, HNF1A loss led to upregulation of transcriptional repressors, providing evidence for a mechanism of transcriptional de-repression through HNF1. CUT&RUN mapping of HNF1 DNA-binding sites in primary human islets verified that a subset of HNF1-regulated genes were direct targets. These data provide unprecedented mechanistic links between HNF1A loss and diabetic phenotypes in mature human and {beta} cells.

genetics↗

A genetic strategy to measure insulin signaling regulation and physiology in Drosophila

Insulin regulation is a hallmark of health, and impaired insulin signaling promotes metabolic diseases like diabetes mellitus. However, current assays for measuring insulin signaling in all animals remain semi-quantitative and lack the sensitivity, tissue-specificity or temporal resolution needed to quantify in vivo physiological signaling dynamics. Insulin signal transduction is remarkably conserved across metazoans, including insulin-dependent phosphorylation and regulation of Akt/Protein kinase B. Here, we generated transgenic fruit flies permitting tissue-specific expression of an immunoepitope-labelled Akt (AktHF). We developed enzyme-linked immunosorption assays (ELISA) to quantify picomolar levels of phosphorylated (pAktHF) and total AktHF in single flies, revealing dynamic tissue-specific physiological regulation of pAktHF in response to fasting and re-feeding, exogenous insulin, or targeted genetic suppression of established insulin signaling regulators. Genetic screening revealed Pp1-87B as an unrecognized regulator of Akt and insulin signaling. Tools and concepts here provide opportunities to discover tissue-specific regulators of in vivo insulin signaling responses. Author SummaryInsulin is an essential hormone that controls metabolism in all animals, by regulating energy use and growth of target tissues. Impaired insulin signaling ("resistance") in humans underlies development of type 2 diabetes, a pandemic disease causing significant morbidity and mortality. The genetic risk for insulin resistance is complex, and studies of diabetes are limited by a lack of tools to measure insulin resistance in a sensitive, quantitative, and tissue-specific way. Here, we describe a new technique to measure the strength of insulin signaling in fruit flies. By combining fruit fly genetics with antibody-based assays, we can quantify phosphorylated Akt, an evolutionarily conserved target of insulin signaling, in specific tissues of the adult fly. We show this technique can detect changes in insulin signaling after fasting and refeeding, addition of exogenous insulin, or genetic disruption of the insulin signaling pathway. We used this method to discover a new regulator of insulin signaling, a phosphatase enzyme encoded by Pp1-87B. This exciting new tool should advance our ability to study and discover additional regulators of insulin signaling and resistance.

genetics↗

Magneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo

Measuring cellular and tissue mechanics inside intact living organisms is essential for interrogating the roles of force in physiological and disease processes, and is a major goal in the field of mechanobiology. However, existing biosensors for 3D tissue mechanics, primarily based on fluorescent emissions and deformable materials, are limited for in vivo measurement due to the limited light penetration and poor material stability inside intact, living organisms. While magneto-motive ultrasound (MMUS), which uses superparamagnetic nanoparticles as imaging contrast agents, has emerged as a promising modality for real-time in vivo imaging of tissue mechanics, it has poor sensitivity and spatiotemporal resolution. To overcome these limitations, we introduce magneto-gas vesicles (MGVs), a unique class of protein nanostructures based on gas vesicles and magnetic nanoparticles that produces differential ultrasound signals in response to varying mechanical properties of surrounding tissues. These hybrid protein nanostructures significantly improve signal strength and detection sensitivity. Furthermore, MGVs enable non-invasive, long-term, and quantitative measurement of mechanical properties within 3D tissues and organs in vivo. We demonstrated the performance of MGV-based mechano-sensors in vitro, in fibrosis models of organoids, and in vivo in mouse liver fibrosis models.

biochemistry↗