Megakaryocytes, the precursors of platelets, are able to detect the stiffness of substrates coated with fibronectin and adapt their shape accordingly, a new study using mouse model-derived cells found. This finding is important because in conditions like myelofibrosis (MF), the bone marrow becomes more rigid, which may affect the shape and function of megakaryocytes.
A study team led by Catherine Leon, PhD, a senior researcher at the French National Institute of Health and Medical Research in Strasbourg, used a polydimethylsiloxane substrate with varying stiffness from physiological to pathological bone marrow and showed that a stiff matrix favored spreading, intracellular contractility, and the assembly of fibronectin fibrils instead of the formation of proplatelets.
The team also demonstrated that the integrin subunit beta-3 (Itgb3) was necessary to sense stiffness.
On the contrary, the researchers showed that soft substrates promoted the formation of proplatelets in an Itgb3-dependent manner.
“Our findings demonstrate the importance of environmental stiffness for megakaryocyte functions with potential physiopathological implications during pathologies that deregulates fibronectin deposition and modulates stiffness in the marrow,” the researchers concluded.
Read more about the different types of MF
MF is a rare condition characterized by bone marrow fibrosis caused by excess fibrous tissue production. This tissue interferes with the normal production of blood cells, leading to symptoms such as anemia, bleeding and bruising, fatigue, bone and joint pain, and splenomegaly.
The exact cause of MF is not well understood, but the disease can be associated with genetic mutations in some cases and secondary to other disorders—such as polycythemia vera, essential thrombocythemia, multiple myeloma, lymphoma, or chronic myeloid leukemia—in others.
The study is published in Blood Advances.
Guinard I, Nguyen T, Brassard-Jollive N, et al. Matrix stiffness controls megakaryocyte adhesion, fibronectin fibrillogenesis and proplatelet formation through Itgβ3. Blood Adv. Published online May 12, 2023. doi:10.1182/bloodadvances.2022008680