Ezgi Antmen | Middle East Technical University (original) (raw)
Papers by Ezgi Antmen
Micromachines
In the recent years, microfabrication technologies have been widely used in cell biology, tissue ... more In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and th...
Advanced biology, 2021
Mechanotransduction proteins transfer mechanical stimuli through nucleo-cytoskeletal coupling and... more Mechanotransduction proteins transfer mechanical stimuli through nucleo-cytoskeletal coupling and affect the nuclear morphology of cancer cells. However, the contribution of actin filament integrity has never been studied directly. It is hypothesized that differences in nuclear deformability of cancer cells are influenced by the integrity of actin filaments. In this study, transparent micropatterned surfaces as simple tools to screen cytoskeletal and nuclear distortions are presented. Surfaces decorated with micropillars are used to culture and image breast cancer cells and quantify their deformation using shape descriptors (circularity, area, perimeter). Using two drugs (cytochalasin D and jasplakinolide), actin filaments are disrupted. Deformation of cells on micropillars is decreased upon drug treatment as shown by increased circularity. However, the effect is much smaller on benign MCF10A than on malignant MCF7 and MDAMB231 cells. On micropatterned surfaces, molecular analysis s...
Objectives Biomaterials are routinely used in clinical applications. A key to the clinical succes... more Objectives Biomaterials are routinely used in clinical applications. A key to the clinical success of implanted biomaterials is not eliciting detrimental immune responses. In this article, we provide an overview of immune responses to biomaterials, along with biomaterial-based approaches to mitigate the adverse host reactions while supporting pro-healing immune responses. We also review existing in-vitro models used to assess the biocompatibility of biomaterials. Key findings Once implanted, biomaterials are often detected as foreign bodies by the immune system, triggering detrimental immune responses. Such responses could damage host tissues and impair the function of implanted materials or devices. Therefore, there is substantial interest in developing new materials and tools with the ability to modulate immune responses to support tissue regeneration and healing processes. However, the bioengineering of immune responses through biomaterials requires detailed understanding of how ...
It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleto... more It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleton are involved in and critical for movement, migration and nuclear positioning of cancer cells. Through nucleo-cytoskeletal coupling, proteins of the LINC complex and the nuclear envelope are capable of transducing cytoplasmic mechanical input across the nuclear membrane; however, their functional importance in the behavior of cancer cells and their nuclei has never been directly tested. In this study, our assumption was that the differences in the malignancies of breast cancer cells are the result of the differences in their nuclear deformation and its expression can be amplified on micropatterned surfaces. Based on this, our hypothesis was that the level of completeness of polymerization of actin filaments can affect nuclear deformability, and as a result, the metastatic capability of the cancer cells. In order to prove this we disrupted the polymerization of the actin filaments by using two drugs, Cytochalasin D and Jasplakinolide, which caused impaired propagation of intracellular forces, prevented nuclear deformation and increased in the expression levels of Lamin A/C and Nesprin-2 in malignant breast cancer cells. Our findings suggest that activity of these two proteins is critical for nucleo-cytoskeletal force transmission. More importantly, actin filament disruption can prevent the distortions in nuclear morphology and as a result avoid the development of cancer metastasis.
Biomaterials Science
Scaffolds are an integral part of the regenerative medicine field. The contact of biomaterials wi... more Scaffolds are an integral part of the regenerative medicine field. The contact of biomaterials with tissue, as was clearly observed over the years, induces immune reactions in a material and...
Bioactive materials, 2018
Cell-substrate interactions play a crucial role in the design of better biomaterials and integrat... more Cell-substrate interactions play a crucial role in the design of better biomaterials and integration of implants with the tissues. Adhesion is the binding process of the cells to the substrate through interactions between the surface molecules of the cell membrane and the substrate. There are several factors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. These factors physically and chemically guide and influence the adhesion strength, spreading, shape and fate of the cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry of substrate surfaces enabling the control of the interaction cells with the substrate. Some of the most commonly used surface engineering methods for eliciting the desired cellular responses on biomaterials are photolithography, electron beam lithography, microcontact printing, and microfluidics. These methods allow production of nano- and micron level substrate features that ...
We produced a three dimensional (3D) bone tumor model (BTM) to study the interactions between hea... more We produced a three dimensional (3D) bone tumor model (BTM) to study the interactions between healthy and tumor cells in a tumor tissue microenvironment, migration of the tumor cells and the efficacy of an anticancer drug, Doxorubicin, for personalized medicine applications. The model consisted of two compartments: (a) a healthy bone tissue mimic, poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (β-TCP) sponge that was seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs), and (b) a tumor mimic, a lyophilized collagen sponge that was seeded with human osteosarcoma cells (Saos-2). The tumor component was introduced to a central cavity created in the healthy bone mimic and together they constituted the total 3D model (3D-BTM). The scaffolds were characterized by determining their mechanical properties, studying their topography and stability with compression tests, microCT, SEM, confocal microscopy and gravimetry. Poro...
Colloids and Surfaces B: Biointerfaces
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 16, 2018
Cell-substrate interactions involve constant probing of microenvironment by cells. One of the res... more Cell-substrate interactions involve constant probing of microenvironment by cells. One of the responses of cells to environmental cues is to change the conformation of their cytoplasm and nucleus. We hypothesized that surface chemistry and topography could be engineered to make these differences significant enough. When designing the substrates that would accentuate these differences, we prepared surfaces carrying cell adhesive biological cues arranged in specific patterns. Collagen type I and poly(lactic acid-co-glycolic acid) (PLGA) were used to represent substrates with biological cues and those without, and these materials were decorated with four square prism micropillars with different dimensions. The nuclear deformations were analyzed using some descriptors. Nucleus area and solidity were the best descriptors in distinguishing the substrates in terms of biological cues, while nucleus area, solidity, and circularity were more sensitive to the interpillar distances. Another dis...
Micromachines
In the recent years, microfabrication technologies have been widely used in cell biology, tissue ... more In the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and th...
Advanced biology, 2021
Mechanotransduction proteins transfer mechanical stimuli through nucleo-cytoskeletal coupling and... more Mechanotransduction proteins transfer mechanical stimuli through nucleo-cytoskeletal coupling and affect the nuclear morphology of cancer cells. However, the contribution of actin filament integrity has never been studied directly. It is hypothesized that differences in nuclear deformability of cancer cells are influenced by the integrity of actin filaments. In this study, transparent micropatterned surfaces as simple tools to screen cytoskeletal and nuclear distortions are presented. Surfaces decorated with micropillars are used to culture and image breast cancer cells and quantify their deformation using shape descriptors (circularity, area, perimeter). Using two drugs (cytochalasin D and jasplakinolide), actin filaments are disrupted. Deformation of cells on micropillars is decreased upon drug treatment as shown by increased circularity. However, the effect is much smaller on benign MCF10A than on malignant MCF7 and MDAMB231 cells. On micropatterned surfaces, molecular analysis s...
Objectives Biomaterials are routinely used in clinical applications. A key to the clinical succes... more Objectives Biomaterials are routinely used in clinical applications. A key to the clinical success of implanted biomaterials is not eliciting detrimental immune responses. In this article, we provide an overview of immune responses to biomaterials, along with biomaterial-based approaches to mitigate the adverse host reactions while supporting pro-healing immune responses. We also review existing in-vitro models used to assess the biocompatibility of biomaterials. Key findings Once implanted, biomaterials are often detected as foreign bodies by the immune system, triggering detrimental immune responses. Such responses could damage host tissues and impair the function of implanted materials or devices. Therefore, there is substantial interest in developing new materials and tools with the ability to modulate immune responses to support tissue regeneration and healing processes. However, the bioengineering of immune responses through biomaterials requires detailed understanding of how ...
It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleto... more It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleton are involved in and critical for movement, migration and nuclear positioning of cancer cells. Through nucleo-cytoskeletal coupling, proteins of the LINC complex and the nuclear envelope are capable of transducing cytoplasmic mechanical input across the nuclear membrane; however, their functional importance in the behavior of cancer cells and their nuclei has never been directly tested. In this study, our assumption was that the differences in the malignancies of breast cancer cells are the result of the differences in their nuclear deformation and its expression can be amplified on micropatterned surfaces. Based on this, our hypothesis was that the level of completeness of polymerization of actin filaments can affect nuclear deformability, and as a result, the metastatic capability of the cancer cells. In order to prove this we disrupted the polymerization of the actin filaments by using two drugs, Cytochalasin D and Jasplakinolide, which caused impaired propagation of intracellular forces, prevented nuclear deformation and increased in the expression levels of Lamin A/C and Nesprin-2 in malignant breast cancer cells. Our findings suggest that activity of these two proteins is critical for nucleo-cytoskeletal force transmission. More importantly, actin filament disruption can prevent the distortions in nuclear morphology and as a result avoid the development of cancer metastasis.
Biomaterials Science
Scaffolds are an integral part of the regenerative medicine field. The contact of biomaterials wi... more Scaffolds are an integral part of the regenerative medicine field. The contact of biomaterials with tissue, as was clearly observed over the years, induces immune reactions in a material and...
Bioactive materials, 2018
Cell-substrate interactions play a crucial role in the design of better biomaterials and integrat... more Cell-substrate interactions play a crucial role in the design of better biomaterials and integration of implants with the tissues. Adhesion is the binding process of the cells to the substrate through interactions between the surface molecules of the cell membrane and the substrate. There are several factors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. These factors physically and chemically guide and influence the adhesion strength, spreading, shape and fate of the cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry of substrate surfaces enabling the control of the interaction cells with the substrate. Some of the most commonly used surface engineering methods for eliciting the desired cellular responses on biomaterials are photolithography, electron beam lithography, microcontact printing, and microfluidics. These methods allow production of nano- and micron level substrate features that ...
We produced a three dimensional (3D) bone tumor model (BTM) to study the interactions between hea... more We produced a three dimensional (3D) bone tumor model (BTM) to study the interactions between healthy and tumor cells in a tumor tissue microenvironment, migration of the tumor cells and the efficacy of an anticancer drug, Doxorubicin, for personalized medicine applications. The model consisted of two compartments: (a) a healthy bone tissue mimic, poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (β-TCP) sponge that was seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs), and (b) a tumor mimic, a lyophilized collagen sponge that was seeded with human osteosarcoma cells (Saos-2). The tumor component was introduced to a central cavity created in the healthy bone mimic and together they constituted the total 3D model (3D-BTM). The scaffolds were characterized by determining their mechanical properties, studying their topography and stability with compression tests, microCT, SEM, confocal microscopy and gravimetry. Poro...
Colloids and Surfaces B: Biointerfaces
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 16, 2018
Cell-substrate interactions involve constant probing of microenvironment by cells. One of the res... more Cell-substrate interactions involve constant probing of microenvironment by cells. One of the responses of cells to environmental cues is to change the conformation of their cytoplasm and nucleus. We hypothesized that surface chemistry and topography could be engineered to make these differences significant enough. When designing the substrates that would accentuate these differences, we prepared surfaces carrying cell adhesive biological cues arranged in specific patterns. Collagen type I and poly(lactic acid-co-glycolic acid) (PLGA) were used to represent substrates with biological cues and those without, and these materials were decorated with four square prism micropillars with different dimensions. The nuclear deformations were analyzed using some descriptors. Nucleus area and solidity were the best descriptors in distinguishing the substrates in terms of biological cues, while nucleus area, solidity, and circularity were more sensitive to the interpillar distances. Another dis...