3D In Vitro Neuron on a Chip for Probing Calcium Mechanostimulation

Abstract

3D cell-to-cell interactions form potentially providing new in vitro approaches to study and mimic the response of biological and cellular processes. One particularly interesting area to study is mechanical stimulation due to its importance in a wide range of physiological systems from cardiac to neural areas. In the neural domain, previous approaches for examining the effects of in vitro mechanical loading on cells have focused mostly on local stimulation of single or multiple neurons cultured on planar substrates. These approaches have proven to be useful for understanding how mechanical stimuli are transduced to biochemical signals including being integrated with micro-fabricated environments. [5-8] While much of the knowledge of cellular biomechanics focuses on our understanding from planar substrates, these 2D systems unfortunately lack physiological aspects such as three dimensionality as well as the complexity of tissue and neuronal function. 3D culture systems can enhance the analysis of integrated interactions between tissue and neural response to recapitulate the natural microenvironment with spatiotemporal details, which may be relevant in understanding many issues including Alzheimer's disease and traumatic brain injury (TBI). [9,10,11] This type of understanding of biomechanics is particularly important as TBI can result from a diversity of situations such as a car crash, an innocuous fall, sports injury, and sudden jolts or blows to the head. Annually these types of issues affect ≈1.5 million people in the United States and 69 million individuals worldwide as well as accounting for one third of all injury-related deaths in the United States affecting every stage of life from adolescents to the elderly. [12,13] Precisely identifying the importance of dysfunction and pathomorphological expressions after external mechanical insult is very important. These responses include a variety of factors such as compressive strains and subcellular responses. The approaches with tissue-on-a-chip systems could help in these areas as representative building blocks for assessing in vitro, multi-dimensional organ architectures toward physiological understanding and treatment. Understanding cell responses under mechanical stimulation can be probed through many techniques. One approach involves an important molecular signature related

Mechanical and Functional Responses in Astrocytes under Alternating Deformation Modes Using Magneto‐Active Substrates

“…[7,8] Several platforms have been developed to study the effects of tissue strain, shear stress, and compression forces on neurons in vitro. [9,10] However, these studies have been technically limited by the inability to apply complex mechanical deformations to soft substrates in a non-invasive, dynamic, and reversible manner. In addition, it is crucial to understand how other brain cells respond to mechanical insults, as their response may directly affect neuronal function and, ultimately, health outcomes.…”

A Programmable Microfluidic Platform to Monitor Calcium Dynamics in Microglia during Inflammation

“…Microfluidic systems are miniaturized and can be automated to deliver treatment to cells and generate a concentration gradient 17 . These systems have recently been used for calcium imaging in different in-vitro models including osteoblasts 18 , neuronal communication [19][20][21] , and astrocyte activation 22 . Additionally, Chokshi et al, introduced an automated microfluidic technology for the in-vivo study of calcium dynamics in Caenorhabditis elegans.…”