Fabrication of Cellular and Extracellular Environments

Cell Printing with DNA and Light

During development and degenerative processes, communication between multiple different cell types along with physicochemical cues from an evolving ECM direct progenitor stem cells to specific lineages. Additionally, complex cell and ligand arrangements along with ECM mechanical properties play a critical role in regulating tissue and cell function.

Interactions between different cell types play an important role in modulating cell function. However, the role of cell-cell signaling in determining cell behavior. remains incompletely understood. We seek to understand how cell architecture alters cell fate through systematic and complete study through the development of enabling technologies.

The Meckes Research group has developed novel methods leveraging light-activated DNA to print cells with spatial control. This research leverages that DNA is an information-rich programmable polymer with specific interactions between complementary DNA. Our group has extended this idea to include site-specific activation of DNA to add an additional layer of control.

Modulatable Materials

The ECM mechanical and chemical properties provide environmental feedback that guides cell fate and directs cell migration. In the case of osteoarthritis, remodeling of the ECM results in changes to mechanical and chemical properties characterized by stiffening and loss of collagen and glycosaminoglycans. Hydrogel systems have been developed that have responsive elements to release growth factors or modulate the bulk properties in order to elicit desired responses (e.g., recellularization/wound healing, differentiation). Despite these advances, mimicking temporal ECM modulation remains challenging, especially when one considers the heterogeneity of the ECM, where a multitude of different proteins organized in nano-to-micro domains modulate cell and tissue function.

Therefore, it is of paramount interest to develop cellular niche models that enable rational temporal control over local mechanics and ligand arrangement with nanoscale precision; such models would enable one to better replicate and study developmental and injury repair processes and develop materials that enhance recellularization and tissue formation. The Meckes group works to develop materials with spatiotemporally arranged properties, which will be used to mimic disease progression and tissue formation processes to determine mechanisms for recellularizing and repairing diseased tissue.

Nanoparticle Discovery Using Biomimetic Models

Modern advancement in materials synthesis has enable the creating of novel platforms that mimick human function. The Meckes resarch group aims to leverage these emerging models to identify nanomaterials that have enhanced properties. What sets us apart from other groups is our focus on including mechanical cues in our models.

Our research program focuses on understanding how the mechanics and formulation of particles is intertwined with one another and how we can leverage disease related mechanical changes to improve potential patient outcomes.

A primary focus of this research endeavor is to understand regulation in lung cancer where mechanical forces play important roles in regulating cancer transitions. In addition, targeting of cancer cells remains challenging. Our goal is to improve delivery efficiency and improve nanoparticle productivity.