Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments

Journal Article · · Biomedical Microdevices
 [1];  [2];  [3];  [4];  [2];  [5]
  1. Univ. of California, Berkeley, CA (United States). NSF Nanoscale Science and Engineering Center (NSEC); Univ. of California, Berkeley, CA (United States). Applied Science and Technology Graduate Program; OSTI
  2. Stanford Univ., CA (United States). Dept. of Materials Science and Engineering
  3. Univ. of California, Berkeley, CA (United States). NSF Nanoscale Science and Engineering Center (NSEC)
  4. Stanford Univ., CA (United States). Dept. of Materials Science and Engineering; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  5. Univ. of California, Berkeley, CA (United States). NSF Nanoscale Science and Engineering Center (NSEC); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division
Spatial patterning of proteins is a valuable technique for many biological applications and is the prevailing tool for defining microenvironments for cells in culture, a required procedure in developmental biology and tissue engineering research. However, it is still challenging to achieve protein patterns that closely mimic native microenvironments, such as gradient protein distributions with desirable mechanical properties. By combining projection dynamic mask lithography and protein engineering with non-canonical photosensitive amino acids, we demonstrate a simple, scalable strategy to fabricate any user-defined 2D or 3D stable gradient pattern with complex geometries from an artificial extracellular matrix (aECM) protein. We show that the elastic modulus and chemical nature of the gradient profile are biocompatible and allow useful applications in cell biological research.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1816134
Journal Information:
Biomedical Microdevices, Journal Name: Biomedical Microdevices Journal Issue: 5 Vol. 11; ISSN 1387-2176
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

References (37)

A digital micro-mirror device-based system for the microfabrication of complex, spatially patterned tissue engineering scaffolds journal January 2006
Multi-analyte immunoassay journal January 1989
A technique for preparing protein gradients on polymeric surfaces: journal May 2005
Projection micro-stereolithography using digital micro-mirror dynamic mask journal May 2005
Determination of Elastic Moduli of Thin Layers of Soft Material Using the Atomic Force Microscope journal May 2002
Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins journal October 2003
Formation of Microscale Gradients of Protein Using Heterobifunctional Photolinkers journal September 1997
Comparative Cell Response to Artificial Extracellular Matrix Proteins Containing the RGD and CS5 Cell-Binding Domains journal January 2004
Cell-Binding Domain Context Affects Cell Behavior on Engineered Proteins journal December 2004
Generation of Solution and Surface Gradients Using Microfluidic Systems journal October 2000
Nanopin Plasmonic Resonator Array and Its Optical Properties journal March 2007
All Optical Interface for Parallel, Remote, and Spatiotemporal Control of Neuronal Activity journal November 2007
Morphogen gradient interpretation journal October 2001
Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning journal June 2003
A photolabile hydrogel for guided three-dimensional cell growth and migration journal March 2004
Engineering tumors with 3D scaffolds journal September 2007
A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues journal January 2008
Model-controlled hydrodynamic focusing to generate multiple overlapping gradients of surface-immobilized proteins in microfluidic devices journal January 2008
Independent tuning of multiple biomaterial properties using protein engineering journal January 2009
Microscale technologies for tissue engineering and biology journal February 2006
Cell Mechanics: Integrating Cell Responses to Mechanical Stimuli journal August 2007
Growth cone navigation in substrate-bound ephrin gradients journal July 2006
Cell guidance by ultrafine topography in vitro journal May 1991
A microfabricated platform probing cytoskeleton dynamics using multidirectional topographical cues journal May 2007
Patterning Cell and Tissue Function journal March 2008
Determination of Elastic Moduli of Thin Layers of Soft Material Using the Atomic Force Microscope journal May 2002
Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins journal October 2003
Micro-stereolithography of polymeric and ceramic microstructures journal October 1999
Micropatterning gradients and controlling surface densities of photoactivatable biomolecules on self-assembled monolayers of oligo(ethylene glycol) alkanethiolates journal October 1997
Protein chip technology journal February 2003
Matrix Elasticity Directs Stem Cell Lineage Specification journal August 2006
Micrometer-Scaled Gradient Surfaces Generated Using Contact Printing of Octadecyltrichlorosilane journal August 2003
Subcellular positioning of small molecules journal June 2001
Massively parallel manipulation of single cells and microparticles using optical images journal July 2005
Model-controlled hydrodynamic focusing to generate multiple overlapping gradients of surface-immobilized proteins in microfluidic devices journal January 2008
Independent tuning of multiple biomaterial properties using protein engineering journal January 2009
Gradients of substrate-bound laminin orient axonal specification of neurons journal September 2002

Cited By (5)

Rapid Fabrication of Complex 3D Extracellular Microenvironments by Dynamic Optical Projection Stereolithography journal July 2012
Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies
  • Chang, Carlos C.; Boland, Eugene D.; Williams, Stuart K.
  • Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 98B, Issue 1 https://doi.org/10.1002/jbm.b.31831
journal April 2011
3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration journal June 2016
Photoreactive elastin-like proteins for use as versatile bioactive materials and surface coatings journal January 2012
Entropic nanothermodynamic potential from molecular trapping within photon induced nano-voids in photon processed PDMS layers journal January 2012

Similar Records

Programmable Chemical Gradient Patterns by Soft Grayscale Lithography
Journal Article · Thu Oct 13 20:00:00 EDT 2011 · Small · OSTI ID:1876049

Designer microenvironments for the analysis of cell and tissue function
Journal Article · Sun Dec 31 23:00:00 EST 1989 · Current Opinion in Cell Biology; (United States) · OSTI ID:7160083

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age
Journal Article · Mon Sep 03 20:00:00 EDT 2018 · Infection and Immunity · OSTI ID:1580337