The Biology of Integration of Cells into Microscale and Nanoscale Systems

In chapter 5 we focused on the informational interface between cells and synthetic components of systems. This interface is concerned with facilitating and manipulating information transport and processing between and within the synthetic and whole-cell components of these hybrid systems. However, there is also a structural interface between these components that is concerned with the physical placement, entrapment, and maintenance of the cells in a manner that enables the informational interface to operate. In this chapter we focus on this structural interface. Successful integration of whole-cell matrices into microscale and nanoscale elements requires a unique environment that fosters continued cell viability while promoting, or at least not blocking, the information transport and communication pathways described in earlier chapters. A century of cell culture has provided a wealth of insight and specific protocols to maintain the viability and (typically) proliferation of virtually every type of organism that can be propagated. More recently, the demands for more efficient bioreactors, more compatible biomedical implants, and the promise of engineered tissues has driven advances in surface-modification sciences, cellular immobilization, and scaffolding that provide structure and control over cell growth, in addition to their basic metabolic requirements. In turn, hybrid biological and electronic systems have emerged, capable of transducing the often highly sensitive and specific responses of cellular matrices for biosensing in environmental, medical, and industrial applications. The demands of these systems have driven advances in cellular immobilization and encapsulation techniques, enabling improved interaction of the biological matrix with its environment while providing nutrient and respiratory requirements for prolonged viability of the living matrices. Predominantly, such devices feature a single interface between the bulk biomatrix and transducer. However, advances in lithography, micromachining, and micro-/nanoscale synthesis provide broader opportunities for interfacing whole-cell matrices with synthetic elements. Advances in engineered, patterned, or directed cell growth are now providing spatial and temporal control over cellular integration within microscale and nanoscale systems. Perhaps the best defined integration of cellular matrices with electronically active substrates has been accomplished with neuronal patterning. Topographical and physicochemical patterning of surfaces promotes the attachment and directed growth of neurites over electrically active substrates that are used to both stimulate and observe excitable cellular activity.