Lamellipodia are crucial for haptotactic sensing and response

Samantha J. King; Sreeja B. Asokan; Elizabeth M. Haynes; Seth P. Zimmerman; Jeremy D. Rotty; James G. Alb; Alicia Tagliatela; Devon R. Blake; Irina P. Lebedeva; Daniel Marston; Heath E. Johnson; Maddy Parsons; Norman E. Sharpless; Brian Kuhlman; Jason M. Haugh; James E. Bear

doi:10.1242/jcs.184507

Lamellipodia are crucial for haptotactic sensing and response

Samantha J. King, Sreeja B. Asokan, Elizabeth M. Haynes, Seth P. Zimmerman, Jeremy D. Rotty, James G. Alb, Alicia Tagliatela, Devon R. Blake, Irina P. Lebedeva, Daniel Marston, Heath E. Johnson, Maddy Parsons, Norman E. Sharpless, Brian Kuhlman, Jason M. Haugh, James E. Bear^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and hasmainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxis - differential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this,we find that expression of the oncogenicRac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments.

Original language	English
Pages (from-to)	2329-2342
Number of pages	14
Journal	Journal of Cell Science
Volume	129
Issue number	12
Early online date	15 Jun 2016
DOIs	https://doi.org/10.1242/jcs.184507
Publication status	E-pub ahead of print - 15 Jun 2016

Keywords

Arp2/3
Directed migration
Haptotaxis
Lamellipodia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lamellipodia are crucial for_KING_Accepted 5May2016_GREEN VoRFinal published version, 3.93 MB

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King, S. J., Asokan, S. B., Haynes, E. M., Zimmerman, S. P., Rotty, J. D., Alb, J. G., Tagliatela, A., Blake, D. R., Lebedeva, I. P., Marston, D., Johnson, H. E., Parsons, M., Sharpless, N. E., Kuhlman, B., Haugh, J. M., & Bear, J. E. (2016). Lamellipodia are crucial for haptotactic sensing and response. Journal of Cell Science, 129(12), 2329-2342. Advance online publication. https://doi.org/10.1242/jcs.184507

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abstract = "Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and hasmainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxis - differential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this,we find that expression of the oncogenicRac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments.",

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AU - Rotty, Jeremy D.

AU - Alb, James G.

AU - Tagliatela, Alicia

AU - Blake, Devon R.

AU - Lebedeva, Irina P.

AU - Marston, Daniel

AU - Johnson, Heath E.

AU - Parsons, Maddy

AU - Sharpless, Norman E.

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AU - Haugh, Jason M.

AU - Bear, James E.

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AB - Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and hasmainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxis - differential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this,we find that expression of the oncogenicRac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments.

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Lamellipodia are crucial for haptotactic sensing and response

Abstract

Keywords

UN SDGs

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