Single cell technologies for monitoring protein secretion heterogeneity.

Cell-to-cell heterogeneity in products secretion is a bottleneck for diverse applications in bioengineering, including controlled drug release, biomaterial assembly, and production of recombinant proteins in bioprocesses. Experimental approaches aiming at characterizing cell-to-cell differences in gene expression and protein accumulation can be partially adapted to address heterogeneity in protein secretion. Significant technological bottlenecks need to be addressed to establish an efficient single cell analysis pipeline. Techniques designed for directing cell collective behavior (e.g., microfluidics or flow cytometry with feedback control) could be adapted for directing product secretion by cells. Cell-to-cell heterogeneity presents challenges across various fields, from biomedicine to bioproduction, where precise cellular responses are vital. While single cell technologies have significantly enhanced our understanding of population heterogeneity, the predominant focus has been on monitoring intracellular compounds. Recognizing the added complexity introduced by the secretion system, in this review, we first provide a systematic overview of the distinct steps necessary for driving protein secretion. We discuss the various sources of noise acting from the synthesized preprotein to the secretory protein released based on a Gram-positive cellular system as a model. We next explore the applicability of single cell technologies for monitoring protein secretion throughout these functional stages. We also emphasize the importance of applying these single cell technologies for monitoring protein secretion during bioproduction. [ABSTRACT FROM AUTHOR]