APL Bioengineering最新文献_第2页

Single-pericyte nanomechanics measured by contraction cytometry. 通过收缩细胞仪测量单个冰细胞的纳米力学。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-08-09 eCollection Date: 2024-09-01 DOI: 10.1063/5.0213761

Md Mydul Islam, Ignas Gaska, Oluwamayokun Oshinowo, Adiya Otumala, Shashank Shekhar, Nicholas Au Yong, David R Myers

{"title":"Single-pericyte nanomechanics measured by contraction cytometry.","authors":"Md Mydul Islam, Ignas Gaska, Oluwamayokun Oshinowo, Adiya Otumala, Shashank Shekhar, Nicholas Au Yong, David R Myers","doi":"10.1063/5.0213761","DOIUrl":"10.1063/5.0213761","url":null,"abstract":"Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile rigor mortis and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036109"},"PeriodicalIF":6.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids. 三维基质硬度可调节口腔鳞状细胞癌球的机械敏感性和表型改变。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-07-31 eCollection Date: 2024-09-01 DOI: 10.1063/5.0210134

Maulee Sheth, Manju Sharma, Maria Lehn, HasanAl Reza, Takanori Takebe, Vinita Takiar, Trisha Wise-Draper, Leyla Esfandiari

{"title":"Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids.","authors":"Maulee Sheth, Manju Sharma, Maria Lehn, HasanAl Reza, Takanori Takebe, Vinita Takiar, Trisha Wise-Draper, Leyla Esfandiari","doi":"10.1063/5.0210134","DOIUrl":"10.1063/5.0210134","url":null,"abstract":"Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how cancer spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving progression. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models, which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. We show that the protein expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 as means to sense changes in static extracellular matrix stiffness, and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036106"},"PeriodicalIF":6.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays. 在微孔阵列抗原感应的控制下，CAR T 细胞渗入三维乳腺癌球形细胞核心并发挥细胞毒性杀伤作用。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-07-23 eCollection Date: 2024-09-01 DOI: 10.1063/5.0207941

Youngbin Cho, Matthew S Laird, Teddi Bishop, Ruxuan Li, Dorota E Jazwinska, Elisa Ruffo, Jason Lohmueller, Ioannis K Zervantonakis

{"title":"CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays.","authors":"Youngbin Cho, Matthew S Laird, Teddi Bishop, Ruxuan Li, Dorota E Jazwinska, Elisa Ruffo, Jason Lohmueller, Ioannis K Zervantonakis","doi":"10.1063/5.0207941","DOIUrl":"10.1063/5.0207941","url":null,"abstract":"The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D breast tumor spheroids and determine predictors of anti-tumor CAR T cell function. To precisely control antigen sensing, we utilized a switchable adaptor CAR system that covalently attaches to co-administered antibody adaptors and mediates antigen recognition. Following the addition of an anti-HER2 adaptor antibody, primary human CAR T cells exhibited higher infiltration, clustering, and secretion of effector cytokines. By tracking CAR T cell killing in individual spheroids, we showed the suppressive effects of spheroid size and identified the initial CAR T cell to spheroid area ratio as a predictor of cytotoxicity. We demonstrate that larger spheroids exhibit higher hypoxia levels and are infiltrated by CAR T cells with a suppressed activation state, characterized by reduced expression of IFN-γ, TNF-α, and granzyme B. Spatiotemporal analysis revealed lower CAR T cell numbers and cytotoxicity in the spheroid core compared to the periphery. Finally, increasing CAR T cell seeding density resulted in higher CAR T cell infiltration and cancer cell elimination in the spheroid core. Our findings provide new quantitative insight into CAR T cell function within 3D cancer spheroids. Given its miniaturized nature and live imaging capabilities, our microfabricated system holds promise for screening cellular immunotherapies.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036105"},"PeriodicalIF":6.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational modeling of the physical features that influence breast cancer invasion into adipose tissue. 对影响乳腺癌侵入脂肪组织的物理特征进行计算建模。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-07-03 eCollection Date: 2024-09-01 DOI: 10.1063/5.0209019

Yitong Zheng, Dong Wang, Garrett Beeghly, Claudia Fischbach, Mark D Shattuck, Corey S O'Hern

{"title":"Computational modeling of the physical features that influence breast cancer invasion into adipose tissue.","authors":"Yitong Zheng, Dong Wang, Garrett Beeghly, Claudia Fischbach, Mark D Shattuck, Corey S O'Hern","doi":"10.1063/5.0209019","DOIUrl":"10.1063/5.0209019","url":null,"abstract":"Breast cancer invasion into adipose tissue strongly influences disease progression and metastasis. The degree of cancer cell invasion into adipose tissue depends on both biochemical signaling and the mechanical properties of cancer cells, adipocytes, and other key components of adipose tissue. We model breast cancer invasion into adipose tissue using discrete element method simulations of active, cohesive spherical particles (cancer cells) invading into confluent packings of deformable polyhedra (adipocytes). We quantify the degree of invasion by calculating the interfacial area At between cancer cells and adipocytes. We determine the long-time value of At vs the activity and strength of the cohesion between cancer cells, as well as the mechanical properties of the adipocytes and extracellular matrix in which adipocytes are embedded. We show that the degree of invasion collapses onto a master curve as a function of the dimensionless energy scale Ec , which grows linearly with the cancer cell velocity persistence time and fluctuations, is inversely proportional to the system pressure, and is offset by the cancer cell cohesive energy. When <math> <mrow> <mrow> <msub><mrow><mi>E</mi></mrow> <mi>c</mi></msub> </mrow> <mo>></mo> <mn>1</mn></mrow> </math> , cancer cells will invade the adipose tissue, whereas for <math> <mrow> <mrow> <msub><mrow><mi>E</mi></mrow> <mi>c</mi></msub> </mrow> <mo><</mo> <mn>1</mn></mrow> </math> , cancer cells and adipocytes remain de-mixed. We also show that At decreases when the adipocytes are constrained by the ECM by an amount that depends on the spatial heterogeneity of the adipose tissue.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036104"},"PeriodicalIF":6.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutual antagonism between CD44 and integrins in glioblastoma cell traction and migration. CD44 和整合素在胶质母细胞瘤细胞牵引和迁移中的相互拮抗作用。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-07-01 eCollection Date: 2024-09-01 DOI: 10.1063/5.0203028

Marcus D Kelly, Matthew R Pawlak, Kevin H Zhan, Ghaidan A Shamsan, Wendy R Gordon, David J Odde

{"title":"Mutual antagonism between CD44 and integrins in glioblastoma cell traction and migration.","authors":"Marcus D Kelly, Matthew R Pawlak, Kevin H Zhan, Ghaidan A Shamsan, Wendy R Gordon, David J Odde","doi":"10.1063/5.0203028","DOIUrl":"10.1063/5.0203028","url":null,"abstract":"Cell migration is the major driver of invasion and metastasis during cancer progression. For cells to migrate, they utilize the actin-myosin cytoskeleton and adhesion molecules, such as integrins and CD44, to generate traction forces in their environment. CD44 primarily binds to hyaluronic acid (HA) and integrins primarily bind to extracellular matrix (ECM) proteins such as collagen. However, the role of CD44 under integrin-mediated conditions and vice versa is not well known. Here, we performed traction force microscopy (TFM) on U251 cells seeded on collagen I-coated polyacrylamide gels to assess the functional mechanical relationship between integrins and CD44. Performing TFM on integrin-mediated adhesion conditions, i.e., collagen, we found that CD44KO U251 cells exerted more traction force than wild-type (WT) U251 cells. Furthermore, untreated WT and CD44-blocked WT exhibited comparable results. Conversely, in CD44-mediated adhesive conditions, integrin-blocked WT cells exerted a higher traction force than untreated WT cells. Our data suggest that CD44 and integrins have a mutually antagonistic relationship where one receptor represses the other's ability to generate traction force on its cognate substrate.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 3","pages":"036102"},"PeriodicalIF":6.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A high throughput cell stretch device for investigating mechanobiology in vitro. 用于研究体外机械生物学的高通量细胞拉伸装置。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-06-26 eCollection Date: 2024-06-01 DOI: 10.1063/5.0206852

Stephen J P Pratt, Christopher M Plunkett, Guray Kuzu, Ton Trinh, Joshua Barbara, Paula Choconta, Doug Quackenbush, Truc Huynh, Anders Smith, S Whitney Barnes, Joel New, James Pierce, John R Walker, James Mainquist, Frederick J King, Jimmy Elliott, Scott Hammack, Rebekah S Decker

{"title":"A high throughput cell stretch device for investigating mechanobiology in vitro.","authors":"Stephen J P Pratt, Christopher M Plunkett, Guray Kuzu, Ton Trinh, Joshua Barbara, Paula Choconta, Doug Quackenbush, Truc Huynh, Anders Smith, S Whitney Barnes, Joel New, James Pierce, John R Walker, James Mainquist, Frederick J King, Jimmy Elliott, Scott Hammack, Rebekah S Decker","doi":"10.1063/5.0206852","DOIUrl":"https://doi.org/10.1063/5.0206852","url":null,"abstract":"Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel in vitro systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026129"},"PeriodicalIF":6.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adsorption of monoclonal antibody fragments at the water-oil interface: A coarse-grained molecular dynamics study. 单克隆抗体片段在水油界面的吸附：粗粒度分子动力学研究。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-06-25 eCollection Date: 2024-06-01 DOI: 10.1063/5.0207959

Suman Saurabh, Li Lei, Zongyi Li, John M Seddon, Jian R Lu, Cavan Kalonia, Fernando Bresme

{"title":"Adsorption of monoclonal antibody fragments at the water-oil interface: A coarse-grained molecular dynamics study.","authors":"Suman Saurabh, Li Lei, Zongyi Li, John M Seddon, Jian R Lu, Cavan Kalonia, Fernando Bresme","doi":"10.1063/5.0207959","DOIUrl":"10.1063/5.0207959","url":null,"abstract":"Monoclonal antibodies (mAbs) can undergo structural changes due to interaction with oil-water interfaces during storage. Such changes can lead to aggregation, resulting in a loss of therapeutic efficacy. Therefore, understanding the microscopic mechanism controlling mAb adsorption is crucial to developing strategies that can minimize the impact of interfaces on the therapeutic properties of mAbs. In this study, we used MARTINI coarse-grained molecular dynamics simulations to investigate the adsorption of the Fab and Fc domains of the monoclonal antibody COE3 at the oil-water interface. Our aim was to determine the regions on the protein surface that drive mAb adsorption. We also investigate the role of protein concentration on protein orientation and protrusion to the oil phase. While our structural analyses compare favorably with recent neutron reflectivity measurements, we observe some differences. Unlike the monolayer at the interface predicted by neutron reflectivity experiments, our simulations indicate the presence of a secondary diffused layer near the interface. We also find that under certain conditions, protein-oil interaction can lead to a considerable distortion in the protein structure, resulting in enhanced adsorption behavior.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026128"},"PeriodicalIF":6.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations. 用于探测人类成纤维细胞从单细胞到群体的实时活化的动态报告器。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-06-24 eCollection Date: 2024-06-01 DOI: 10.1063/5.0166152

Samantha E Cassel, Breanna M Huntington, Wilfred Chen, Pedro Lei, Stelios T Andreadis, April M Kloxin

{"title":"Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations.","authors":"Samantha E Cassel, Breanna M Huntington, Wilfred Chen, Pedro Lei, Stelios T Andreadis, April M Kloxin","doi":"10.1063/5.0166152","DOIUrl":"10.1063/5.0166152","url":null,"abstract":"Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human in vitro model systems complement in vivo animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms. This work established approaches for assessing the temporal dynamics of these responses using genetically encoded fluorescent reporters of alpha smooth muscle actin expression, an indicator of fibroblast activation. Specifically, we created a toolset of human lung fibroblast reporter cell lines from different origins (male, female; healthy, idiopathic pulmonary fibrosis) and used three different versions of the reporter with the fluorescent protein modified to exhibit different temporal stabilities, providing temporal resolution of protein expression processes over a range of timescales. Using this toolset, we demonstrated that reporters provide insight into population shifts in response to both mechanical and biochemical cues that are not detectable by traditional end point assessments with differential responses based on cell origin. Furthermore, individual cells can also be tracked over time, with opportunities for comparison to complementary end point measurements. The establishment of this reporter toolset enables dynamic cell investigations that can be translated into more complex synthetic culture environments for elucidating disease mechanisms and evaluating therapeutics for lung fibrosis and other complex biological processes more broadly.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026127"},"PeriodicalIF":6.6,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multicompartment duct platform to study epithelial-endothelial crosstalk associated with lung adenocarcinoma. 研究与肺腺癌相关的上皮-内皮串联的多室导管平台。

IF 6.6 3区医学

APL Bioengineering Pub Date : 2024-06-17 eCollection Date: 2024-06-01 DOI: 10.1063/5.0207228

Keith A Gagnon, Jessie Huang, Olivia T Hix, Veronica W Hui, Anne Hinds, Esther Bullitt, Jeroen Eyckmans, Darrell N Kotton, Christopher S Chen

{"title":"Multicompartment duct platform to study epithelial-endothelial crosstalk associated with lung adenocarcinoma.","authors":"Keith A Gagnon, Jessie Huang, Olivia T Hix, Veronica W Hui, Anne Hinds, Esther Bullitt, Jeroen Eyckmans, Darrell N Kotton, Christopher S Chen","doi":"10.1063/5.0207228","DOIUrl":"10.1063/5.0207228","url":null,"abstract":"Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in which human induced pluripotent stem cell-derived alveolar epithelial type II cells (iAT2s) form polarized duct-like lumens alongside engineered perfused vessels lined with human umbilical vein endothelium, all within a 3D, physiologically relevant microenvironment. Using this model, we investigated the morphologic and signaling consequences of the KRASG12D mutation, a commonly identified oncogene in human lung adenocarcinoma (LUAD). We show that expression of the mutant KRASG12D isoform in iAT2s leads to a hyperproliferative response and morphologic dysregulation in the epithelial monolayer. Interestingly, the mutant epithelia also drive an angiogenic response in the adjacent vasculature that is mediated by enhanced secretion of the pro-angiogenic factor soluble uPAR. These results demonstrate the functionality of a multi-cellular in vitro platform capable of modeling mutation-specific behavioral and signaling changes associated with lung adenocarcinoma.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026126"},"PeriodicalIF":6.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parallel on-chip micropipettes enabling quantitative multiplexed characterization of vesicle mechanics and cell aggregates rheology. 可对囊泡力学和细胞聚集流变学进行定量多路复用表征的并行芯片上微量移液器。

IF 6 3区医学

APL Bioengineering Pub Date : 2024-06-12 eCollection Date: 2024-06-01 DOI: 10.1063/5.0193333

Sylvain Landiech, Marianne Elias, Pierre Lapèze, Hajar Ajiyel, Marine Plancke, Blanca González-Bermúdez, Adrian Laborde, Fabien Mesnilgrente, David Bourrier, Debora Berti, Costanza Montis, Laurent Mazenq, Jérémy Baldo, Clément Roux, Morgan Delarue, Pierre Joseph

{"title":"Parallel on-chip micropipettes enabling quantitative multiplexed characterization of vesicle mechanics and cell aggregates rheology.","authors":"Sylvain Landiech, Marianne Elias, Pierre Lapèze, Hajar Ajiyel, Marine Plancke, Blanca González-Bermúdez, Adrian Laborde, Fabien Mesnilgrente, David Bourrier, Debora Berti, Costanza Montis, Laurent Mazenq, Jérémy Baldo, Clément Roux, Morgan Delarue, Pierre Joseph","doi":"10.1063/5.0193333","DOIUrl":"10.1063/5.0193333","url":null,"abstract":"Micropipette aspiration (MPA) is one of the gold standards for quantifying biological samples' mechanical properties, which are crucial from the cell membrane scale to the multicellular tissue. However, relying on the manipulation of individual home-made glass pipettes, MPA suffers from low throughput and no automation. Here, we introduce the sliding insert micropipette aspiration method, which permits parallelization and automation, thanks to the insertion of tubular pipettes, obtained by photolithography, within microfluidic channels. We show its application both at the lipid bilayer level, by probing vesicles to measure membrane bending and stretching moduli, and at the tissue level by quantifying the viscoelasticity of 3D cell aggregates. This approach opens the way to high-throughput, quantitative mechanical testing of many types of biological samples, from vesicles and individual cells to cell aggregates and explants, under dynamic physico-chemical stimuli.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026122"},"PeriodicalIF":6.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0