Focus Review

Subject Category: Biopolymers, Bio-related Polymer Materials

Polymer Journal (2014) 46, 524–536; doi:10.1038/pj.2014.20; published online 23 April 2014

Control of extracellular microenvironments using polymer/protein nanofilms for the development of three-dimensional human tissue chips

Michiya Matsusaki1 and Mitsuru Akashi1

1Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan

Correspondence: Professor M Akashi, Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail:

Received 6 January 2014; Revised 6 February 2014; Accepted 17 February 2014
Advance online publication 23 April 2014



Cell functions, such as adhesion, migration, proliferation, differentiation, organization, protein expression and death, are dynamically regulated at the surface of cell membranes by the interaction between a ligand molecule of the cellular microenvironments and the membrane protein receptors. Furthermore, physical signals of cellular microenvironments, stiffness, elasticity and hydration, are also important factors for the modulation of cellular functions. In the body, natural extracellular matrices (ECMs) and ECM-bound growth factors regulate cell functions. The universal control of cell functions at the single-cell level through the artificial modulation of extracellular microenvironments by mimicking the natural ECMs would be a key technique for biomedical fields. In the present review, the fabrication of nanometer-sized artificial ECM films using various polymers and proteins on single-cell surfaces to control cell functions is described. The thickness, charge and component of the ECM films were observed to significantly affect the cell functions. Moreover, the optimized ECM films induced cell–cell organization to construct three-dimensional human tissue chips. Control of extracellular microenvironments using a nanometer-sized polymer/protein film as an artificial ECM would be useful as a novel technique to regulate cell functions as desired.


cell; layer-by-layer; nanofilms; tissue engineering