Many cell types communicate by means of dendritic
extensions via a multi-tiered set of geometric and chemical cues.
Until recently, mimicking the compartmentalized in vivo cellular
environment of dendrite-expressing cells such as osteocytes and
motor neurons in a spatially and temporally controllable manner
was limited by the challenges of in vitro device fabrication at
submicron scales. Utilizing the improved resolution of current
fabrication technology, we have designed a multiscale device,
the Macro-micro-nano system, or Mμn, composed of two dis-
tinct cell-seeding and interrogation compartments separated by a
nanochannel array. The array enables dendrite ingrowth, while
providing a mechanism for fluidic sequestration and/or
temporally-mediated diffusible signaling between cell popula-
tions. Modeling of the Mμn system predicted the ability to iso-
late diffusible signals, namely ATP. Empirical diffusion studies
verified computational modeling. In addition, cell viability, den-
drite interaction with the nanoarray, and cellular purinergic re-
sponse to heat shock were experimentally evaluated within the
device for both osteocytes and motor neurons. Our results de-
scribe a novel in vitro system in which dendrite-expressing cell
types can be studied within nano-environments that mimic
in vivo conditions. In particular, the Mμn system enables real-
time observation of cell to cell communication between cell
populations in distinct, but fluidically coupled regions.

• A multiscale fluidic device for the study of dendrite-mediated cell to cell communication