RESUMEN
Whilst demonstrated extensively in vitro, the control of cell behaviour via modulation of substrate compliance in live tissues has not been accomplished to date. Here we propose that stem cells can be regulated solely through in situ modulation of tissue biomechanics. By first establishing, via high-resolution Brillouin spectro-microscopy, that the outer edge (limbus) of live human corneas has a substantially lower bulk modulus compared to their centre, we then demonstrate that this difference is associated with limbal epithelial stem cell (LESC) residence and YAP-dependent mechanotransduction. This phenotype-through-biomechanics correlation is further explored in vivo using a rabbit alkali burn model. Specifically, we show that treating the burnt surface of the cornea with collagenase effectively restores the tissue's mechanical properties and its capacity to support LESCs through mechanisms involving YAP suppression. Overall, these findings have extended implications for understanding stem cell niche biomechanics and its impact on tissue regeneration.
Asunto(s)
Córnea/citología , Limbo de la Córnea/citología , Células Madre/citología , Adulto , Anciano , Animales , Fenómenos Biomecánicos , Diferenciación Celular/fisiología , Colagenasas/farmacología , Córnea/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/trasplante , Humanos , Limbo de la Córnea/efectos de los fármacos , Limbo de la Córnea/ultraestructura , Mecanotransducción Celular , Microscopía Fluorescente , Persona de Mediana Edad , Fenotipo , Conejos , Nicho de Células Madre/efectos de los fármacos , Nicho de Células Madre/fisiología , Células Madre/efectos de los fármacos , Ingeniería de Tejidos/métodos , Cicatrización de Heridas/fisiologíaRESUMEN
A new Brillouin spectro-microscope was designed and built to investigate the mechanical properties of bovine and human corneas. This instrument integrates a single-stage virtually imaged phased array spectrometer with a novel adaptive-optics interferometric filter to achieve unprecedented rejection of the elastic background signal. As a result, highly-resolved, reproducible data from both thin and thick collagen-based materials were obtained. In particular, this technique is capable of rigorously measuring the relative stiffness of different areas of human corneas, thus providing a true non-contact method to characterise the fundamental mechanical features of both live and fixed biological tissue samples.
Asunto(s)
Córnea/diagnóstico por imagen , Córnea/fisiología , Microscopía/instrumentación , Microscopía/métodos , Anciano , Animales , Bovinos , Córnea/anatomía & histología , Femenino , Humanos , Interferometría/métodos , Masculino , Espectrometría de Masas/instrumentación , Espectrometría de Masas/métodos , Persona de Mediana Edad , Fijación del TejidoRESUMEN
We present results from the first field-trial of a quantum-secured DWDM transmission system, in which quantum key distribution (QKD) is combined with 4 × 10 Gb/s encrypted data and transmitted simultaneously over 26 km of field installed fiber. QKD is used to frequently refresh the key for AES-256 encryption of the 10 Gb/s data traffic. Scalability to over 40 DWDM channels is analyzed.
