Cellular and molecular bioengineering最新文献

{"title":"A Model for Chemomechanical Coupling of Kinesin-3 Motor","authors":"Ping Xie","doi":"10.1007/s12195-024-00795-1","DOIUrl":"https://doi.org/10.1007/s12195-024-00795-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Kinesin-3 motor, which is in the monomeric and inactive form in solution, after cargo-induced dimerization can step on microtubules towards the plus end with a high velocity and a supperprocessivity, which is responsible for transporting the cargo in axons and dendrites. The kinesin-3 motor has a large initial landing rate to microtubules and spends the majority of its stepping cycle in a one-head-bound state. Under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To understand the physical origin of the peculiar features for the kinesin-3 motor, a model is presented here for its chemomechanical coupling. Based on the model the dynamics of the motor under no load, under the ramping load and under the constant load is studied analytically.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The theoretical results explain well the available experimental data under no load and under the ramping load. For comparison, the corresponding available experimental data for the kinesin-1 motor under the ramping load are also explained. The predicted results of the velocity, dissociation rate and run length versus the constant load for the kinesin-3 motor are provided.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The study has strong implications for the chemomechanical coupling mechanism of the kinesin-3 dimer. The origin of the kinesin-3 dimer in the predominant one-head-bound state is due to the fact that the rate of ATP transition to ADP in the trailing head is much larger than that of ADP release from the MT-bound head. The study shows that the kinesin-3 ADP-head has an evidently longer interaction distance with microtubule than the kinesin-1 ADP-head, explaining why in the initial ADP state the kinesin-3 motor has the much larger landing rate than the kinesin-1 motor and why under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139902865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Hematocrit Level and Integrin αIIbβIII Function on vWF-Mediated Platelet Adhesion and Shear-Induced Platelet Aggregation in a Sudden Expansion","authors":"","doi":"10.1007/s12195-024-00796-0","DOIUrl":"https://doi.org/10.1007/s12195-024-00796-0","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Purpose</h3> <p>Shear-mediated thrombosis is a clinically relevant phenomenon that underlies excessive arterial thrombosis and device-induced thrombosis. Red blood cells are known to mechanically contribute to physiological hemostasis through margination of platelets and vWF, facilitating the unfurling of vWF multimers, and increasing the fraction of thrombus-contacting platelets. Shear also plays a role in this phenomenon, increasing both the degree of margination and the near-wall forces experienced by vWF and platelets leading to unfurling and activation. Despite this, the contribution of red blood cells in shear-induced platelet aggregation has not been fully investigated—specifically the effect of elevated hematocrit has not yet been demonstrated.</p> </span> <span> <h3>Methods</h3> <p>Here, a microfluidic model of a sudden expansion is presented as a platform for investigating platelet adhesion at hematocrits ranging from 0 to 60% and shear rates ranging from 1000 to 10,000 s⁻¹. The sudden expansion geometry models nonphysiological flow separation characteristic to mechanical circulatory support devices, and the validatory framework of the FDA benchmark nozzle. PDMS microchannels were fabricated and coated with human collagen. Platelets were fluorescently tagged, and blood was reconstituted at variable hematocrit prior to perfusion experiments. Integrin function of selected blood samples was inhibited by a blocking antibody, and platelet adhesion and aggregation over the course of perfusion was monitored.</p> </span> <span> <h3>Results</h3> <p>Increasing shear rates at physiological and elevated hematocrit levels facilitate robust platelet adhesion and formation of large aggregates. Shear-induced platelet aggregation is demonstrated to be dependent on both α_IIbβ_III function and the presence of red blood cells. Inhibition of α_IIbβ_III results in an 86.4% reduction in overall platelet adhesion and an 85.7% reduction in thrombus size at 20-60% hematocrit. Hematocrit levels of 20% are inadequate for effective platelet margination and subsequent vWF tethering, resulting in notable decreases in platelet adhesion at 5000 and 10,000 s^-1 compared to 40% and 60%. Inhibition of α_IIbβ_III triggered dramatic reductions in overall thrombus coverage and large aggregate formation. Stability of platelets tethered by vWF are demonstrated to be α_IIbβ_III-dependent, as adhesion of single platelets treated with A2A9, an anti-α_IIbβ_III blocking antibody, is transient and did not lead to sustained thrombus formation.</p> </span> <span> <h3>Conclusions</h3> <p>This study highlights driving factors in vWF-mediated platelet adhesion that are relevant to clinical suppression of shear-induced thrombosis and in vitro assays of platelet adhesion. Primarily, increasing hematocrit promotes platelet margination, permit","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurogenic Cell Behavior in 3D Culture Enhanced Within a Highly Compliant Synthetic Hydrogel Platform Formed via Competitive Crosslinking","authors":"","doi":"10.1007/s12195-024-00794-2","DOIUrl":"https://doi.org/10.1007/s12195-024-00794-2","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Purpose</h3> <p>Scaffold materials that better support neurogenesis are still needed to improve cell therapy outcomes for neural tissue damage. We have used a modularly tunable, highly compliant, degradable hydrogel to explore the impacts of hydrogel compliance stiffness on neural differentiation. Here we implemented competitive matrix crosslinking mechanics to finely tune synthetic hydrogel moduli within soft tissue stiffnesses, a range much softer than typically achievable in synthetic crosslinked hydrogels, providing a modularly controlled and ultrasoft 3D culture model which supports and enhances neurogenic cell behavior.</p> </span> <span> <h3>Methods</h3> <p>Soluble competitive allyl monomers were mixed with proteolytically-degradable poly(ethylene glycol) diacrylate derivatives and crosslinked to form a matrix, and resultant hydrogel stiffness and diffusive properties were evaluated. Neural PC12 cells or primary rat fetal neural stem cells (NSCs) were encapsulated within the hydrogels, and cell morphology and phenotype were investigated to understand cell-matrix interactions and the effects of environmental stiffness on neural cell behavior within this model.</p> </span> <span> <h3>Results</h3> <p>Addition of allyl monomers caused a concentration-dependent decrease in hydrogel compressive modulus from 4.40 kPa to 0.26 kPa (natural neural tissue stiffness) without influencing soluble protein diffusion kinetics through the gel matrix. PC12 cells encapsulated in the softest hydrogels showed significantly enhanced neurite extension in comparison to PC12s in all other hydrogel stiffnesses tested. Encapsulated neural stem cells demonstrated significantly greater spreading and elongation in 0.26 kPa alloc hydrogels than in 4.4 kPa hydrogels. When soluble growth factor deprivation (for promotion of neural differentiation) was evaluated within the neural stiffness gels (0.26 kPa), NSCs showed increased neuronal marker expression, indicating early enhancement of neurogenic differentiation.</p> </span> <span> <h3>Conclusions</h3> <p>Implementing allyl-acrylate crosslinking competition reduced synthetic hydrogel stiffness to provide a supportive environment for 3D neural tissue culture, resulting in enhanced neurogenic behavior of encapsulated cells. These results indicate the potential suitability of this ultrasoft hydrogel system as a model platform for further investigating environmental factors on neural cell behavior.</p> </span>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporation of ChatGPT and Other Large Language Models into a Graduate Level Computational Bioengineering Course","authors":"Michael R. King, Adam M. Abdulrahman, Mark I. Petrovic, Patricia L. Poley, Sarah P. Hall, Surat Kulapatana, Zachary E. Lamantia","doi":"10.1007/s12195-024-00793-3","DOIUrl":"https://doi.org/10.1007/s12195-024-00793-3","url":null,"abstract":"<p>The remarkable capabilities of generative artificial intelligence and large language models (LLMs) such as ChatGPT have delighted users around the world. Educators have regarded these tools as either a cause for great concern, an opportunity to educate students on cutting-edge technology, or often some combination of the two. Throughout the Fall 2023 semester, we explored the use of ChatGPT (and Bard, among other LLMs) in a graduate level numerical and statistical methods course for PhD-level bioengineers. In this article we share examples of this ChatGPT content, our observations on what worked best in our course, and speculate on how bioengineering students may be best served by this technology in the future.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relatively Rare Populations of Invasive Cells Drive Progression of Heterogeneous Tumors","authors":"Susan E. Leggett, Molly C. Brennan, Sophia Martinez, Joe Tien, Celeste M. Nelson","doi":"10.1007/s12195-023-00792-w","DOIUrl":"https://doi.org/10.1007/s12195-023-00792-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Breast tumors often display an astonishing degree of spatial and temporal heterogeneity, which are associated with cancer progression, drug resistance, and relapse. Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous subtype for which targeted therapies are scarce. Consequently, patients with TNBC have a poorer overall prognosis compared to other breast cancer patients. Within heterogeneous tumors, individual clonal subpopulations may exhibit differences in their rates of growth and degrees of invasiveness. We hypothesized that such phenotypic heterogeneity at the single-cell level may accelerate tumor progression by enhancing the overall growth and invasion of the entire tumor.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To test this hypothesis, we isolated and characterized clonal subpopulations with distinct morphologies and biomarker expression from the inherently heterogeneous 4T1 mouse mammary carcinoma cell line. We then leveraged a 3D microfluidic tumor model to reverse-engineer intratumoral heterogeneity and thus investigate how interactions between phenotypically distinct subpopulations affect tumor growth and invasion.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We found that the growth and invasion of multiclonal tumors were largely dictated by the presence of cells with epithelial and mesenchymal traits, respectively. The latter accelerated overall tumor invasion, even when these cells comprised less than 1% of the initial population. Consistently, tumor progression was delayed by selectively targeting the mesenchymal subpopulation.</p><h3 data-test=\"abstract-sub-heading\">Discussion</h3><p>This work reveals that highly invasive cells can dominate tumor phenotype and that specifically targeting these cells can slow the progression of heterogeneous tumors, which may help inform therapeutic approaches.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trisomy 21 Alters Cell Proliferation and Migration of iPSC-Derived Cardiomyocytes on Type VI Collagen","authors":"Rachel S. Reeser, Alyssa K. Salazar, Kendra M. Prutton, James R. Roede, Mitchell C. VeDepo, Jeffrey G. Jacot","doi":"10.1007/s12195-023-00791-x","DOIUrl":"https://doi.org/10.1007/s12195-023-00791-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Individuals with Down syndrome (DS) are 2000 times more likely to develop a congenital heart defect (CHD) than the typical population Freeman et al. in Am J Med Genet 80:213–217 (1998). The majority of CHDs in individuals with DS characteristically involve the atrioventricular (AV) canal, including the valves and the atrial or ventricular septum. Type VI collagen (COLVI) is the primary structural component in the developing septa and endocardial cushions, with two of the three genes encoding for COLVI located on human chromosome 21 and upregulated in Down syndrome (von Kaisenberg et al. in Obstet Gynecol 91:319–323, 1998; Gittenberger-De Groot et al. in Anatom Rec Part A 275:1109–1116, 2023).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To investigate the effect of COLVI dosage on cardiomyocytes with trisomy 21, induced pluripotent stem cells (iPSC) from individuals with DS and age- and sex-matched controls were differentiated into cardiomyocytes (iPSC-CM) and plated on varying concentrations of COLVI.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Real time quantitative PCR showed decreased expression of cardiac-specific genes of DS iPSC-CM lines compared to control iPSC-CM. As expected, DS iPSC-CM had increased expression of genes on chromosome 21, including <i>COL6A1</i>, <i>COL6A2</i>, as well as genes not located on chromosome 21, namely <i>COL6A3</i>, <i>HAS2</i> and <i>HYAL2</i>. We found that higher concentrations of COLVI result in decreased proliferation and migration of DS iPSC-CM, but not control iPSC-CM.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These results suggest that the increased expression of COLVI in DS may result in lower migration-driven elongation of endocardial cushions stemming from lower cell proliferation and migration, possibly contributing to the high incidence of CHD in the DS population.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139093636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Influence of Heterogeneity Within Cell Types on Microvessel Network Transport","authors":"Junyu Nan, Sayan Roychowdhury, Amanda Randles","doi":"10.1007/s12195-023-00790-y","DOIUrl":"https://doi.org/10.1007/s12195-023-00790-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Current research on the biophysics of circulating tumor cells often overlooks the heterogeneity of cell populations, focusing instead on average cellular properties. This study aims to address the gap by considering the diversity of cell biophysical characteristics and their implications on cancer spread.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We utilized computer simulations to assess the influence of variations in cell size and membrane elasticity on the behavior of cells within fluid environments. The study controlled cell and fluid properties to systematically investigate the transport of tumor cells through a simulated network of branching channels.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The simulations revealed that even minor differences in cellular properties, such as slight changes in cell radius or shear elastic modulus, lead to significant changes in the fluid conditions that cells experience, including velocity and wall shear stress (p &lt; 0.001).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The findings underscore the importance of considering cell heterogeneity in biophysical studies and suggest that small variations in cellular characteristics can profoundly impact the dynamics of tumor cell circulation. This has potential implications for understanding the mechanisms of cancer metastasis and the development of therapeutic strategies.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138513702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens","authors":"Sue Ann Mah, Recep Avci, Jean-Marie Vanderwinden, Peng Du","doi":"10.1007/s12195-023-00789-5","DOIUrl":"https://doi.org/10.1007/s12195-023-00789-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Several functional gastrointestinal disorders (FGIDs) have been associated with the degradation or remodeling of the network of interstitial cells of Cajal (ICC). Introducing fractal analysis to the field of gastroenterology as a promising data analytics approach to extract key structural characteristics that may provide insightful features for machine learning applications in disease diagnostics. Fractal geometry has advantages over several physically based parameters (or classical metrics) for analysis of intricate and complex microstructures that could be applied to ICC networks.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, three fractal structural parameters: Fractal Dimension, Lacunarity, and Succolarity were employed to characterize scale-invariant complexity, heterogeneity, and anisotropy; respectively of three types of gastric ICC network structures from a flat-mount transgenic mouse stomach.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The Fractal Dimension of ICC in the longitudinal muscle layer was found to be significantly lower than ICC in the myenteric plexus and circumferential muscle in the proximal, and distal antrum, respectively (both p &lt; 0.0001). Conversely, the Lacunarity parameters for ICC-LM and ICC-CM were found to be significantly higher than ICC-MP in the proximal and in the distal antrum, respectively (both p &lt; 0.0001). The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum (p &lt; 0.05).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The fractal parameters presented here could go beyond the limitation of classical metrics to provide better understanding of the structural-functional relationship between ICC networks and the conduction of gastric bioelectrical slow waves.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138513691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 2023 CMBE Young Innovators: ChatGPT Gets the Final Word","authors":"Alisa Morss Clyne, Owen J. T. McCarty, Michael R. King","doi":"10.1007/s12195-023-00788-6","DOIUrl":"https://doi.org/10.1007/s12195-023-00788-6","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136023224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Head-to-Head Comparison of CCN4, DNMT3A, PTPN11, and SPARC as Suppressors of Anti-tumor Immunity","authors":"Anika C. Pirkey, Wentao Deng, Danielle Norman, Atefeh Razazan, David J. Klinke","doi":"10.1007/s12195-023-00787-7","DOIUrl":"https://doi.org/10.1007/s12195-023-00787-7","url":null,"abstract":"","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}