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Credit: Andre E.X. Brown
Platelets can sense and respond to their surroundings, according to research published in PNAS.
Researchers reported that platelets can detect mechanical aspects of their environment and transduce those cues into biological signals.
Experiments showed that platelets could sense the stiffness of a fibrin/fibrinogen substrate, and increasing stiffness was associated with increased platelet adhesion, spreading, and activation.
“Platelets are smarter than we give them credit for, in that they are able to sense the physical characteristics of their environment and respond in a graduated way,” said study author Wilbur Lam, MD, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
He and his colleagues were able to separate physical and biochemical effects on platelet behavior by forming polymer gels with different degrees of stiffness and then overlaying each with the same coating of fibrinogen.
With stiffer gels, the researchers observed an increase in platelet adhesion, spreading, and activation. This behavior was most pronounced when the concentration of fibrinogen was relatively low.
“This variability helps to explain platelet behavior in the 3D context of a clot in the body, which can be quite heterogenous in makeup,” Dr Lam said.
The researchers were also able to dissect platelet biochemistry by allowing the platelets to adhere and then spread on the various gels under the influence of drugs that interfere with different biochemical steps.
The team found that integrins, which engage the fibrinogen, and the protein Rac1 are involved in the initial mechanical sensing during adhesion. Myosin and actin, components of the cytoskeleton, are responsible for platelet spreading.
“We found that the initial adhesion and later spreading are separable, because different biochemical pathways are involved in each step,” Dr Lam said. “Our data show that mechanosensing can occur and plays important roles even when the cellular structural building blocks are fairly basic, even when the nucleus is absent.”
The researchers believe these findings could influence the design of medical devices, as modifying the stiffness of materials used in these devices might reduce the formation of blood clots. The results could also guide the refinement of anticoagulant therapy. 
Credit: Andre E.X. Brown
Platelets can sense and respond to their surroundings, according to research published in PNAS.
Researchers reported that platelets can detect mechanical aspects of their environment and transduce those cues into biological signals.
Experiments showed that platelets could sense the stiffness of a fibrin/fibrinogen substrate, and increasing stiffness was associated with increased platelet adhesion, spreading, and activation.
“Platelets are smarter than we give them credit for, in that they are able to sense the physical characteristics of their environment and respond in a graduated way,” said study author Wilbur Lam, MD, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
He and his colleagues were able to separate physical and biochemical effects on platelet behavior by forming polymer gels with different degrees of stiffness and then overlaying each with the same coating of fibrinogen.
With stiffer gels, the researchers observed an increase in platelet adhesion, spreading, and activation. This behavior was most pronounced when the concentration of fibrinogen was relatively low.
“This variability helps to explain platelet behavior in the 3D context of a clot in the body, which can be quite heterogenous in makeup,” Dr Lam said.
The researchers were also able to dissect platelet biochemistry by allowing the platelets to adhere and then spread on the various gels under the influence of drugs that interfere with different biochemical steps.
The team found that integrins, which engage the fibrinogen, and the protein Rac1 are involved in the initial mechanical sensing during adhesion. Myosin and actin, components of the cytoskeleton, are responsible for platelet spreading.
“We found that the initial adhesion and later spreading are separable, because different biochemical pathways are involved in each step,” Dr Lam said. “Our data show that mechanosensing can occur and plays important roles even when the cellular structural building blocks are fairly basic, even when the nucleus is absent.”
The researchers believe these findings could influence the design of medical devices, as modifying the stiffness of materials used in these devices might reduce the formation of blood clots. The results could also guide the refinement of anticoagulant therapy.
Credit: Andre E.X. Brown
Platelets can sense and respond to their surroundings, according to research published in PNAS.
Researchers reported that platelets can detect mechanical aspects of their environment and transduce those cues into biological signals.
Experiments showed that platelets could sense the stiffness of a fibrin/fibrinogen substrate, and increasing stiffness was associated with increased platelet adhesion, spreading, and activation.
“Platelets are smarter than we give them credit for, in that they are able to sense the physical characteristics of their environment and respond in a graduated way,” said study author Wilbur Lam, MD, PhD, of the Emory University School of Medicine in Atlanta, Georgia.
He and his colleagues were able to separate physical and biochemical effects on platelet behavior by forming polymer gels with different degrees of stiffness and then overlaying each with the same coating of fibrinogen.
With stiffer gels, the researchers observed an increase in platelet adhesion, spreading, and activation. This behavior was most pronounced when the concentration of fibrinogen was relatively low.
“This variability helps to explain platelet behavior in the 3D context of a clot in the body, which can be quite heterogenous in makeup,” Dr Lam said.
The researchers were also able to dissect platelet biochemistry by allowing the platelets to adhere and then spread on the various gels under the influence of drugs that interfere with different biochemical steps.
The team found that integrins, which engage the fibrinogen, and the protein Rac1 are involved in the initial mechanical sensing during adhesion. Myosin and actin, components of the cytoskeleton, are responsible for platelet spreading.
“We found that the initial adhesion and later spreading are separable, because different biochemical pathways are involved in each step,” Dr Lam said. “Our data show that mechanosensing can occur and plays important roles even when the cellular structural building blocks are fairly basic, even when the nucleus is absent.”
The researchers believe these findings could influence the design of medical devices, as modifying the stiffness of materials used in these devices might reduce the formation of blood clots. The results could also guide the refinement of anticoagulant therapy.