Differential dynamics of platelet contact and spreading.
Platelet spreading is critical for hemostatic plug formation and thrombosis. However, the detailed dynamics of platelet spreading as a function of receptor-ligand adhesive interactions has not been thoroughly investigated. Using reflection interference contrast microscopy, we found that both adhesive interactions and PAR4 activation affect the dynamics of platelet membrane contact formation during spreading. The initial growth of close contact area during spreading was controlled by the combination of different immobilized ligands or PAR4 activation on fibrinogen, whereas the growth of the total area of spreading was independent of adhesion type and PAR4 signaling. We found that filopodia extend to their maximal length and then contract over time; and that filopodial protrusion and expansion were affected by PAR4 signaling. Upon PAR4 activation, the integrin α(IIb)β(3) mediated close contact to fibrinogen substrata and led to the formation of ringlike patterns in the platelet contact zone. A systematic study of platelet spreading of GPVI-, α(2)-, or β(3)-deficient platelets on collagen or fibrinogen suggests the integrin α(2) is indispensable for spreading on collagen. The platelet collagen receptors GPVI and α(2) regulate integrin α(IIb)β(3)-mediated platelet spreading on fibrinogen. This work elucidates quantitatively how receptor-ligand adhesion and biochemical signals synergistically control platelet spreading.
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Dooyoung
D
Lee
Karen P
KP
Fong
Michael R
MR
King
Lawrence F
LF
Brass
Daniel A
DA
Hammer
D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008853:Microscopy; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D015398:Signal Transduction
D016023:Integrins; D008024:Ligands; D010980:Platelet Membrane Glycoproteins; D044462:Receptors, Proteinase-Activated; C098341:platelet membrane glycoprotein VI; D005340:Fibrinogen