RESUMEN
Rheological characterization of cells using passive particle tracking techniques can yield substantial information regarding local cellular material properties. However, limited work has been done to establish the changes in material properties of mechanically-responsive cells that experience external stimuli. In this study, cardiac fibroblasts plated on either fibronectin or collagen were treated with cytochalasin, mechanically stretched, or both, and their trajectories and complex moduli were extracted. Results demonstrate that both solid and fluid components were altered by such treatments in a receptor-dependent manner, and that, interestingly, cells treated with cytochalasin were still capable of stiffening in response to mechanical stimuli despite gross stress fiber disruption. These results suggest that the material properties of cells are dependent on a variety of environmental cues and can provide insight into physiological and disease processes.
Asunto(s)
Fibroblastos/fisiología , Corazón/fisiología , Estrés Mecánico , Animales , Células Cultivadas , Colágeno , Citocalasina D/farmacología , Fibroblastos/efectos de los fármacos , Fibronectinas , Ratas , ReologíaRESUMEN
BACKGROUND: There is an increasing need to understand cell-cell interactions for cell and tissue engineering purposes, such as optimizing cell sheet constructs, as well as for examining adhesion defect diseases. For cell-sheet engineering, one major obstacle to sheet function is that cell sheets in suspension are fragile and, over time, will contract. While the role of the cytoskeleton in maintaining the structure and adhesion of cells cultured on a rigid substrate is well-characterized, a systematic examination of the role played by different components of the cytoskeleton in regulating cell sheet contraction and cohesion in the absence of a substrate has been lacking. RESULTS: In this study, keratinocytes were cultured until confluent and cell sheets were generated using dispase to remove the influence of the substrate. The effects of disrupting actin, microtubules or intermediate filaments on cell-cell interactions were assessed by measuring cell sheet cohesion and contraction. Keratin intermediate filament disruption caused comparable effects on cell sheet cohesion and contraction, when compared to actin or microtubule disruption. Interfering with actomyosin contraction demonstrated that interfering with cell contraction can also diminish cell cohesion. CONCLUSIONS: All components of the cytoskeleton are involved in maintaining cell sheet cohesion and contraction, although not to the same extent. These findings demonstrate that substrate-free cell sheet biomechanical properties are dependent on the integrity of the cytoskeleton network.
Asunto(s)
Citoesqueleto/metabolismo , Ingeniería de Tejidos , Actinas/metabolismo , Línea Celular , Humanos , Queratina-14/antagonistas & inhibidores , Queratina-14/genética , Queratina-14/metabolismo , Queratina-5/antagonistas & inhibidores , Queratina-5/genética , Queratina-5/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Microtúbulos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
We report the case of a 3-year-old boy who presented with recurrent stereotyped transient episodes of left sided weakness consistent with capsular warning syndrome (CWS) which eventually progressed to acute ischemic stroke (AIS). He received thrombolytic therapy with tissue plasminogen activator. Workup was notable for positive CSF varicella (VZV) PCR, and positive CSF and serum VZV IgG and negative IgM. On further history, he was unvaccinated and had a rash consistent with VZV 5 months prior to presentation. This case highlights the importance of recognizing CWS given the increased risk of progression to AIS. In addition, it emphasizes the importance of considering VZV vasculopathy in pediatric AIS and inquiring about infectious history and immunization status despite high rates of vaccination in the United States.
RESUMEN
Coronavirus disease 2019 (COVID-19) usually leads to a mild infectious disease course in children, but serious complications may occur in conjunction with both acute infection and associated phenomena such as the multisystem inflammatory syndrome in children (MIS-C). Neurological symptoms, which have been predominantly reported in adults, range from mild headache to seizure, peripheral neuropathy, stroke, demyelinating disorders, and encephalopathy. Similar to respiratory and cardiac manifestations of COVID-19, neurological complications present differently based on age and underlying comorbidities. This review provides a concise overview of the neurological conditions seen in the context of COVID-19, as well as potential mechanisms and long-term implications of COVID-19 in the pediatric population from literature reviews and primary data collected at NewYork-Presbyterian Morgan Stanley Children's Hospital.