Making Every Cell Matter

Alginate hydrogels – which are derived from the polysaccharide found in brown seaweed – have emerged as an effective material for manipulating cells and tissues due to their biocompatibility and the ability to tune their mechanical and biochemical properties to match physiological conditions found inside the body.

Already they have been demonstrated to influence the differentiation of stem cells, incite immune attacks on cancer cells, and weaken tumors’ resistance to chemotherapy, but as of yet, hydrogels have mostly been useful for controlling groups of cells at large rather than individual cells. For example, alginate capsules filled with hundreds of pancreatic islet cells can be implanted in diabetic patients. However, these capsules are millimeters in size and eventually become surrounded by thick scar tissue that blocks the biological signals of islet cells and renders the implant ineffective.

Now, thanks to the joint efforts of a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), a new and highly effective microfluidic method for encapsulating single cells in microscale hydrogels sets the stage for a dramatic increase in the specificity of control that can be exerted upon cells and their ability to survive implantation. The research was reported October 31 in the scientific journal Nature Materials. 

“There’s been a tremendous amount of work to try and understand how biomaterials can determine cell function and fate, but the majority of that work has been done in populations of cells,” said David Mooney, Ph.D., a Wyss Core Faculty member and the Robert P. Pinkas Family Professor of Bioengineering at SEAS, who is the corresponding author on the new study. “With this work, we take everything we have learned and take it down to the single cell level, enabling us to influence cell behavior on a whole different scale.”

Mooney teamed with fellow Wyss Core Faculty member David Weitz, Ph.D., who is the Mallingkrodt Professor of Physics and Applied Sciences at Harvard University and SEAS and who is co-author on the study, to achieve the novel microfluidic-based method for encapsulating single cells within microgel capsules. The co-first authors on the study are Angelo Mao, a graduate researcher at Wyss and SEAS, and Jae-Won Shin, Ph.D., who was formerly a Wyss Institute Postdoctoral Fellow and is currently Assistant Professor of Pharmacology and Bioengineering at University of Illinois at Chicago.

“This is an exciting and important extension of cell-based biomaterials to the level of single cells, which can then serve both as a precise building block for larger cell structures and as a means of investigating the behavior at the level of single cells, providing unprecedented insight into cell function and properties,” said Weitz.