Theoretical and experimental investigation of spatial temperature gradient effects on cells using a microfabricated microheater platform

Abstract

While the cellular interaction with the chemical microenvironment has been studied in detail in the past, the effect of thermal signals and gradients on cells is not well understood. While almost all biological macrosystems exhibit temperature sensitivity, this has not been studied much at the cellular level. The capability of precise control of temperature and heat flux at the scale of a few microns using microfabricated structures makes microelectromechanical systems (MEMS) ideal for investigating these effects. This work describes a MEMS-based microheater platform capable of subjecting surface-adhered cells to microscale temperature gradients. This microdevice comprises a free-standing thin film based microheater platform. The design and microfabrication of this microdevice are described. A thermal conduction model is developed in order to thermally characterize the microheater platform. Protocols for culturing cells on the microheater platform are developed, making it possible to adhere cells on the microheater surface and subject them to a desired spatial temperature gradient. Experiments demonstrating the spatial control of cell viability using the microheater device are described. This is followed by experiments that explore the possibility of cellular growth in response to thermal gradients, similar to chemotaxis. Thermotactic effect is well known at the organismal level. However, cells used in this work did not exhibit any thermotactic effect. A theoretical model for predicting cell response to a spatial temperature gradient in its microenvironment is proposed. The model is based on the effect of the temperature gradient on the chemical sensory process of the cell. The model predicts that in addition to the thermal gradient, the thermotactic effect also depends on a number of other parameters that have not been well characterized in the past. The microheater platform described in this work offers a fundamental new experimental tool with which to explore the interaction of cellular systems with their thermal microenvironment. The theoretical model of thermotaxis developed here furthers the understanding of the function of a cell as a thermal and chemical sensor.