Neurite branch retraction is caused by a threshold-dependent mechanical impact.
Recent results indicate that, in addition to chemical cues, mechanical stimuli may also impact neuronal growth. For instance, unlike most other cell types, neurons prefer soft substrates. However, the mechanisms responsible for the neuronal affinity for soft substrates have not yet been identified. In this study, we show that, in vitro, neurons continuously probe their mechanical environment. Growth cones visibly deform substrates with a compliance commensurate with their own. To understand the sensing of stiff substrates by growth cones, we investigated their precise temporal response to well-defined mechanical stress. When the applied stress exceeded a threshold of 274 +/- 41 pN/microm(2), neurons retracted and re-extended their processes, thereby enabling exploration of alternative directions. A calcium influx through stretch-activated ion channels and the detachment of adhesion sites were prerequisites for this retraction. Our data illustrate how growing neurons may detect and avoid stiff substrates--as a mechanism involved in axonal branch pruning--and provide what we believe is novel support of the idea that mechanics may act as guidance cue for neuronal growth.
Department of Physics, Soft Matter Physics Group, Paul Flechsig Institute of Brain Research, Universität Leipzig, Leipzig, Germany. kf284@cam.ac.uk
Kristian
K
Franze
Jens
J
Gerdelmann
Michael
M
Weick
Timo
T
Betz
Steve
S
Pawlizak
Melike
M
Lakadamyali
Johannes
J
Bayer
Katja
K
Rillich
Michael
M
Gögler
Yun-Bi
YB
Lu
Andreas
A
Reichenbach
Paul
P
Janmey
Josef
J
Käs
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D007473:Ion Channels / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical
D007473:Ion Channels; D002118:Calcium