The cell can be thought of as a collection of organelles enclosed in a larger membrane compartment that separates the cell interior from the exterior. These organelles are akin to the “unit operations” in a chemical plant and carry out specific processes that are integrated, coordinated, and efficient to maintain life. Cell membranes localize and orchestrate these critical cellular processes and reactions, through compartmentation and spatio-temporal organization within these organelles. In this work, we aimed to build synthetic cellular processes on chip to re-create the organizational structure of the cell and its biochemical processes. We envision a two-dimensional “cell” comprised of microfluidic compartments that contain the biomembranes, enzymes, and other elements necessary to carry out biochemical processes as they do in cellular organelles. We take a modular approach where there is a mapping of the cell’s organelle structure to the microfluidic devices and these devices, in turn, are arranged to carry out a sequence of reactions/processes to produce a desired outcome. In ongoing work, our team has devised a three-stage device: one chamber synthesizes a protein (akin to the ribosome), a second chamber transfers a pre-made glycan onto the synthesized protein to “posttranslationally modify” it (akin to the endoplasmic reticulum), and a third chamber captures (and later releases) the final product. In parallel, we are working on devices to carry out the sequential process of creating the glycan itself from monosaccharide building units (akin to the Golgi apparatus). Bringing these chambers together in an integrated manner allows the production and posttranslational modification of a protein in a cell-free manner. The beauty of the approach is that later we can rearrange the order of reactions to create non-native posttranslational modifications that cannot be produced in the live cell, but that may have high value as a therapeutic or biomaterial. Besides this advantage, this 2D “cell” may also allow us to answer questions about the “Rules of Life.”
Susan Daniel is an Associate Professor of Chemical and Biomolecular Engineering at Cornell University. Her research interests are in understanding phenomena at biological interfaces and chemically patterned surfaces that interact with soft matter – liquids; polymers; and biological materials, like cells, viruses, proteins, and lipids. In particular, her work focuses on understanding cell membrane organization, structure, and function. She leads a biotechnology research group that pioneered the use of “biomembrane chips” as a cell-free platform to conduct studies of the interactions between viruses and host cells that has elucidated how these interactions lead to virus infection. Her group’s most recent work leverages biomembrane chips to create synthetic cellular posttranslational modifications in “organelles-on-a-chip” to produce therapeutic biomolecules. Finally, her group has combined the biomembrane chip platform with conducting polymers to create a new class of bioelectronic-membrane sensing platform for studies of transmembrane protein function. Given the highly interdisciplinary research conducted in her team, Susan believes that access to education for all people is necessary to cultivate the creativity and excellence required to solve today’s pressing problems and she is committed to the promotion of inclusive and empowering environments in education and research. Susan’s work has garnered a number of recognitions, including an NSF CAREER award (2011), the Schwartz Life Sciences award (2016), and in 2017, she was honored with the College of Engineering’s Research Excellence Award. Susan holds a BS, MS and PhD from Lehigh University in Bethlehem, PA, USA.