title: Stem cell membrane engineering for cell rolling using peptide conjugation and tuning of cell-selectin interaction kinetics.
abstract: Dynamic cell-microenvironment interactions regulate many biological events and play a critical role in tissue regeneration. Cell homing to targeted tissues requires well balanced interactions between cells and adhesion molecules on blood vessel walls. However, many stem cells lack affinity with adhesion molecules. It is challenging and clinically important to engineer these stem cells to modulate their dynamic interactions with blood vessels. In this study, a new chemical strategy was developed to engineer cell-microenvironment interactions. This method allowed the conjugation of peptides onto stem cell membranes without affecting cell viability, proliferation or multipotency. Mesenchymal stem cells (MSCs) engineered in this manner showed controlled firm adhesion and rolling on E-selectin under physiological shear stresses. For the first time, these biomechanical responses were achieved by tuning the binding kinetics of the peptide-selectin interaction. Rolling of engineered MSCs on E-selectin is mediated by a Ca(2+) independent interaction, a mechanism that differs from the Ca(2+) dependent physiological process. This further illustrates the ability of this approach to manipulate cell-microenvironment interactions, in particular for the application of delivering cells to targeted tissues. It also provides a new platform to engineer cells with multiple functionalities.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: Marta
authors.initials: M
authors.lastname: Byrska-Bishop
authors.forename: Cathy T
authors.initials: CT
authors.lastname: Zhang
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
authors.forename: Albert K
authors.initials: AK
authors.lastname: Tai
authors.forename: Won Woo
authors.initials: WW
authors.lastname: Lee
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xu
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D007700:Kinetics; D044085:Microfluidics; D010455:Peptides / Q000378:metabolism*; D019087:Selectins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering
chemical_list: D010455:Peptides; D019087:Selectins