title: Technical advance: introducing a novel metric, directionality time, to quantify human neutrophil chemotaxis as a function of matrix composition and stiffness.
abstract: A direct consequence of cellular movement and navigation, migration incorporates elements of speed, direction, and persistence of motion. Current techniques to parameterize the trajectory of a chemotaxing cell most commonly pair migration speed with some measure of persistence by calculating MSD, RMS speed, TAD, and/or CI. We address inherent limitations in TAD and CI for comparative analysis by introducing two new analytical tools to quantify persistence: directionality index and directionality time. With the use of these tools, we show that the mechanical properties of the underlying substrate contribute significantly to the regulation of human neutrophil chemotaxis toward fMLP on Fgn-, Col-, and Fn-coated gels of varying elasticity. The β₁-integrin ligand Col demonstrated mechanosensitive speed. In contrast, β₂-integrin ligand Fgn supported mechanosensitive persistence. Fn, recognized by β₁ and β₂ integrins, mechanoregulated speed and persistence. Blocking β₂ integrins of cells migrating on Fn identified an underlying β₂-integrin-directed modulation of persistence. These data demonstrate that individual components of the neutrophil chemotactic response show integrin dependence and are finely tunable with different ligand, mechanotactic, and chemotactic cues, underscoring the need for sensitive analytical methods.
authors: Division of Surgical Research, Department of Surgery, Rhode Island Hospital, and the Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; and xianobrien@gmail.com.
authors: Xian M
authors: XM
authors: O'Brien
authors: Department of Physics and.
authors: Alex J
authors: AJ
authors: Loosley
authors: Division of Surgical Research, Department of Surgery, Rhode Island Hospital, and the Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; and Graduate Program in Pathobiology, Brown University, Providence, Rhode Island, USA.
authors: Katie E
authors: KE
authors: Oakley
authors: Department of Physics and.
authors: Jay X
authors: JX
authors: Tang
authors: Division of Surgical Research, Department of Surgery, Rhode Island Hospital, and the Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA; and.
authors: Jonathan S
authors: JS
authors: Reichner
mesh_terms: D018821:CD18 Antigens / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D003094:Collagen / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000502:physiology
chemical_list: D018821:CD18 Antigens; D005353:Fibronectins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003094:Collagen
keywords: biophysics; integrins; mechanosensing; migration