UCLA

Biomechanical properties, such as cellular stiffness and cell-generating force, play pivotal roles in mechanotransduction, the process cells sense, adapt and respond to external stimuli in their surrounding microenvironments. They are critical biomarkers that can indicate the physiological states and molecular configurations of cells. Despite its promising scope, existing technologies for mapping large-area biomechanical properties are still limited, mostly restricted by the small field of view and scanning nature of traditional traction force microscopy (TFM). On the other hand, for a multicellular system to function properly, dynamic equilibrium and coordinated interplays between biomechanical, biochemical, and bioelectrical properties are crucial. Chaotic activities of either of these properties can break the equilibrium, subsequently interrupting the associated downstream events, and can even lead to fatal failure of the whole system. Therefore, the capability to perform real-time monitoring of dynamic changes can provide groundbreaking insights into the bidirectional interactions in biological systems.In this dissertation, a novel platform for mapping large-area biomechanical dynamics is proposed, designed, and established. The platform utilizes a massive number of optical diffractive elements embedded periodically in an elastic membrane to track the traction force generated by the cells seeded on top. Observation field of view up to 10.6 mm by 10.6 mm is achieved, which is 3 orders of magnitude improvement compared to traditional TFM. Meanwhile, high spatiotemporal resolution is maintained, allowing us to measure transient activities at cellular level. To demonstrate the capabilities of our platform for visualizing the large-area biomechanical dynamics in real-time, monolayer tissue composed of millions of neonatal rat ventricular myocytes (NRVMs) are seeded on our devices. For the first time, global trend and local heterogeneities of mechanical waves created by cardiac beatings of NRVMs are recorded concurrently with unprecedented details. Conduction patterns, activation time, activation durations, conduction velocities and dominant frequencies are analyzed temporally and spatially. In addition, several conditions, including spontaneous beating, electrical stimulation, and chemical stimulation are conducted. The results further highlight our platform’s potential for biological applications such as drug screening and pathological studies. Moreover, the label-free feature of our platform introduces minimized interruption to the physiological activities of cells, thereby extending the observation time of experiments. Recordings of biomechanical dynamics from the same NRVM cultures up to 7 days are reported. This is a dramatic enhancement compared to conventional optical mapping using fluorescent dyes, which often has hours-long observation window. Lastly, we integrated the platform with a fluorescent imaging system to conduct simultaneous mappings of the calcium ion concentration and biomechanical dynamics resulting from the cardiac beating of NRVMs. It is the first demonstration of detailed mechanical wave propagation and the corresponding calcium ion transient. Our innovative approach holds promise for studying the complex interplay between biomechanical, biochemical, and bioelectrical properties in biological systems.