語系:
繁體中文
English
說明(常見問題)
回圖書館首頁
手機版館藏查詢
登入
回首頁
切換:
標籤
|
MARC模式
|
ISBD
FindBook
Google Book
Amazon
博客來
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors./
作者:
Sonmez, Utku M.
面頁冊數:
1 online resource (190 pages)
附註:
Source: Dissertations Abstracts International, Volume: 84-03, Section: B.
Contained By:
Dissertations Abstracts International84-03B.
標題:
Bioengineering. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29252427click for full text (PQDT)
ISBN:
9798351459493
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors.
Sonmez, Utku M.
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors.
- 1 online resource (190 pages)
Source: Dissertations Abstracts International, Volume: 84-03, Section: B.
Thesis (Ph.D.)--Carnegie Mellon University, 2022.
Includes bibliographical references
Mechanical cues are one of the most important biophysical regulators of cellular machinery under both physiological and pathophysiological conditions. Advancements in the microtechnology in the last two decades allowed researchers to develop automated, high-throughput, and multifunctional experimental tools based on microfluidic techniques in order to facilitate conventional mechanobiological experiments and enable novel experimental paradigms that would not be possible otherwise. In this work, we developed various microfluidic devices and techniques that can be used to generate different mechanical microenvironments for the understanding of the role of mechanical cues at the cellular level.Suspended mammalian cells such as lymphocytes constantly migrate within the tissues following the complex patterns of chemokine gradients in order to carry out diverse immune system functions. The in vitro analysis of the immune cell migration under precisely controlled microenvironments have a potential to enable in-depth understanding of the mechanism that regulate immune cell motility behaviors. However, in order to unveil the cell migration through cellular locomotion suspended immune cells should be isolated from external mechanical forces such as shear stress dependent drag forces. Therefore, we generated a microfluidic flow-free gradient generator system and used this approach with Jurkat cells to analyze their motion patterns within various CXCL12 gradients and extracellular matrix configuration. Using this system, we found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. Moreover, we the observed that the chemotaxis of Jurkat cells was governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Moreover, we developed a framework where the distinct migratory behaviors in response to chemokine gradients in different contexts might be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Lastly, we used this system with primary murine CD8+ T cells obtained from either healthy mice or B16 mouse tumor model in order investigate effect of tumor microenvironment in T cell motility.Another example of the biological phenomena where mechanics plays an important role is development. Drosophila melanogaster (fruit fly) is a well-established model organism which has been used in developmental biology studies for over a century. Although most of the Drosophila research largely focused on biochemistry and genetics as the regulatory mechanisms for development, recent studies showed that both internally and externally generated mechanical signals also play an important role during development. In this regard, we developed a novel microfluidic system for automatically aligning and loading hundreds of Drosophila embryos into microchannels where they can be simultaneously compressed to desired levels using pneumatically actuated deformable sidewalls. Using this microsystem, we demonstrated the effect of different levels of acute and chronic compression on the developmental progression and viability of the Drosophila embryos. Furthermore, we quantitatively characterized dose- and time-dependent induction of the ectopic expression of Twist -a crucial transcription factor that governs gastrulation process- upon mechanical compression.One of most mechanically sensitive cell type in mammalian body is the endothelial cells -monolayer of which constitutes the inner wall of the vasculature- as they are constantly subjected to mechanical cues in the form of blood shear stress. We further enhanced the scope of this work by developing a novel microfluidic system that can generate various physiologically relevant shear stress modalities such as different levels of shear stress and shear stress gradients for the investigation of endothelial cell polarity and orientation in response to flow which is considered to be a marker for endothelial dysfunction. In this microfluidic device, human umbilical vein endothelial cells (HUVECs) exhibited a rapid and robust response to shear stress, with the relative positioning of the Golgi and nucleus transitioning from non-polarized to polarized in a shear stress magnitude- and gradient-independent manner. By contrast, polarized HUVECs oriented their Golgi and nucleus polarity to the flow vector in a shear stress magnitude-dependent manner, with positive shear stress gradients inhibiting and negative shear stress gradients promoting this upstream orientation.Lastly, we developed a new microfabrication technique called Polycarbonate Heat Molding (PCH molding) that can facilitate the fabrication of microfluidic devices. We tested this technique with master molds fabricated through photolithography, mechanical micromilling as well as 3D printing. Using this technique, we were able to successfully copy microstructures with submicron feature sizes and high aspect ratios. We characterized the copying fidelity of this technique and tested mechanically active microfluidic devices fabricated via PCH molding. We also used this approach to combine different master molds with up to 19 unique geometries into a single monolithic copy mold in a single step displaying the effectiveness of the copying technique over a large footprint area to scale up the microfabrication. This novel microfabrication technique can be performed outside the cleanroom without using any sophisticated equipment, suggesting a simple way for high-throughput rigid monolithic mold fabrication that can be used in mechanobiological studies.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023
Mode of access: World Wide Web
ISBN: 9798351459493Subjects--Topical Terms:
657580
Bioengineering.
Subjects--Index Terms:
Cell migrationIndex Terms--Genre/Form:
542853
Electronic books.
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors.
LDR
:07164nmm a2200409K 4500
001
2356755
005
20230619080105.5
006
m o d
007
cr mn ---uuuuu
008
241011s2022 xx obm 000 0 eng d
020
$a
9798351459493
035
$a
(MiAaPQ)AAI29252427
035
$a
AAI29252427
040
$a
MiAaPQ
$b
eng
$c
MiAaPQ
$d
NTU
100
1
$a
Sonmez, Utku M.
$3
3697253
245
1 0
$a
Controlling the Physical Microenvironment of Cells with Microfluidics for Studying Mechanically Regulated Cellular Behaviors.
264
0
$c
2022
300
$a
1 online resource (190 pages)
336
$a
text
$b
txt
$2
rdacontent
337
$a
computer
$b
c
$2
rdamedia
338
$a
online resource
$b
cr
$2
rdacarrier
500
$a
Source: Dissertations Abstracts International, Volume: 84-03, Section: B.
500
$a
Advisor: LeDuc, Philip.
502
$a
Thesis (Ph.D.)--Carnegie Mellon University, 2022.
504
$a
Includes bibliographical references
520
$a
Mechanical cues are one of the most important biophysical regulators of cellular machinery under both physiological and pathophysiological conditions. Advancements in the microtechnology in the last two decades allowed researchers to develop automated, high-throughput, and multifunctional experimental tools based on microfluidic techniques in order to facilitate conventional mechanobiological experiments and enable novel experimental paradigms that would not be possible otherwise. In this work, we developed various microfluidic devices and techniques that can be used to generate different mechanical microenvironments for the understanding of the role of mechanical cues at the cellular level.Suspended mammalian cells such as lymphocytes constantly migrate within the tissues following the complex patterns of chemokine gradients in order to carry out diverse immune system functions. The in vitro analysis of the immune cell migration under precisely controlled microenvironments have a potential to enable in-depth understanding of the mechanism that regulate immune cell motility behaviors. However, in order to unveil the cell migration through cellular locomotion suspended immune cells should be isolated from external mechanical forces such as shear stress dependent drag forces. Therefore, we generated a microfluidic flow-free gradient generator system and used this approach with Jurkat cells to analyze their motion patterns within various CXCL12 gradients and extracellular matrix configuration. Using this system, we found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. Moreover, we the observed that the chemotaxis of Jurkat cells was governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Moreover, we developed a framework where the distinct migratory behaviors in response to chemokine gradients in different contexts might be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Lastly, we used this system with primary murine CD8+ T cells obtained from either healthy mice or B16 mouse tumor model in order investigate effect of tumor microenvironment in T cell motility.Another example of the biological phenomena where mechanics plays an important role is development. Drosophila melanogaster (fruit fly) is a well-established model organism which has been used in developmental biology studies for over a century. Although most of the Drosophila research largely focused on biochemistry and genetics as the regulatory mechanisms for development, recent studies showed that both internally and externally generated mechanical signals also play an important role during development. In this regard, we developed a novel microfluidic system for automatically aligning and loading hundreds of Drosophila embryos into microchannels where they can be simultaneously compressed to desired levels using pneumatically actuated deformable sidewalls. Using this microsystem, we demonstrated the effect of different levels of acute and chronic compression on the developmental progression and viability of the Drosophila embryos. Furthermore, we quantitatively characterized dose- and time-dependent induction of the ectopic expression of Twist -a crucial transcription factor that governs gastrulation process- upon mechanical compression.One of most mechanically sensitive cell type in mammalian body is the endothelial cells -monolayer of which constitutes the inner wall of the vasculature- as they are constantly subjected to mechanical cues in the form of blood shear stress. We further enhanced the scope of this work by developing a novel microfluidic system that can generate various physiologically relevant shear stress modalities such as different levels of shear stress and shear stress gradients for the investigation of endothelial cell polarity and orientation in response to flow which is considered to be a marker for endothelial dysfunction. In this microfluidic device, human umbilical vein endothelial cells (HUVECs) exhibited a rapid and robust response to shear stress, with the relative positioning of the Golgi and nucleus transitioning from non-polarized to polarized in a shear stress magnitude- and gradient-independent manner. By contrast, polarized HUVECs oriented their Golgi and nucleus polarity to the flow vector in a shear stress magnitude-dependent manner, with positive shear stress gradients inhibiting and negative shear stress gradients promoting this upstream orientation.Lastly, we developed a new microfabrication technique called Polycarbonate Heat Molding (PCH molding) that can facilitate the fabrication of microfluidic devices. We tested this technique with master molds fabricated through photolithography, mechanical micromilling as well as 3D printing. Using this technique, we were able to successfully copy microstructures with submicron feature sizes and high aspect ratios. We characterized the copying fidelity of this technique and tested mechanically active microfluidic devices fabricated via PCH molding. We also used this approach to combine different master molds with up to 19 unique geometries into a single monolithic copy mold in a single step displaying the effectiveness of the copying technique over a large footprint area to scale up the microfabrication. This novel microfabrication technique can be performed outside the cleanroom without using any sophisticated equipment, suggesting a simple way for high-throughput rigid monolithic mold fabrication that can be used in mechanobiological studies.
533
$a
Electronic reproduction.
$b
Ann Arbor, Mich. :
$c
ProQuest,
$d
2023
538
$a
Mode of access: World Wide Web
650
4
$a
Bioengineering.
$3
657580
650
4
$a
Biomechanics.
$3
548685
650
4
$a
Biophysics.
$3
518360
650
4
$a
Mechanical engineering.
$3
649730
653
$a
Cell migration
653
$a
Mechanobiology
653
$a
MEMS
653
$a
Microfabrication
653
$a
Microfluidics
655
7
$a
Electronic books.
$2
lcsh
$3
542853
690
$a
0202
690
$a
0648
690
$a
0786
690
$a
0548
710
2
$a
ProQuest Information and Learning Co.
$3
783688
710
2
$a
Carnegie Mellon University.
$b
Mechanical Engineering.
$3
2096240
773
0
$t
Dissertations Abstracts International
$g
84-03B.
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29252427
$z
click for full text (PQDT)
筆 0 讀者評論
館藏地:
全部
電子資源
出版年:
卷號:
館藏
1 筆 • 頁數 1 •
1
條碼號
典藏地名稱
館藏流通類別
資料類型
索書號
使用類型
借閱狀態
預約狀態
備註欄
附件
W9479111
電子資源
11.線上閱覽_V
電子書
EB
一般使用(Normal)
在架
0
1 筆 • 頁數 1 •
1
多媒體
評論
新增評論
分享你的心得
Export
取書館
處理中
...
變更密碼
登入